diff --git a/pandas/_libs/src/vendored/ujson/lib/ultrajsonenc.c b/pandas/_libs/src/vendored/ujson/lib/ultrajsonenc.c
index e3e710ce1b876..942bd0b518144 100644
--- a/pandas/_libs/src/vendored/ujson/lib/ultrajsonenc.c
+++ b/pandas/_libs/src/vendored/ujson/lib/ultrajsonenc.c
@@ -44,6 +44,7 @@ Numeric decoder derived from TCL library
 #include <float.h>
 #include <locale.h>
 #include <math.h>
+#include <stdint.h>
 #include <stdio.h>
 #include <stdlib.h>
 #include <string.h>
@@ -763,7 +764,12 @@ void Buffer_AppendIntUnchecked(JSONObjectEncoder *enc, JSINT32 value) {
 
 void Buffer_AppendLongUnchecked(JSONObjectEncoder *enc, JSINT64 value) {
     char *wstr;
-    JSUINT64 uvalue = (value < 0) ? -value : value;
+    JSUINT64 uvalue;
+    if (value == INT64_MIN) {
+      uvalue = INT64_MAX + UINT64_C(1);
+    } else {
+      uvalue = (value < 0) ? -value : value;
+    }
 
     wstr = enc->offset;
     // Conversion. Number is reversed.
diff --git a/pandas/_libs/tslibs/np_datetime.pyx b/pandas/_libs/tslibs/np_datetime.pyx
index 7b2ee68c73ad2..c3ee68e14a8d4 100644
--- a/pandas/_libs/tslibs/np_datetime.pyx
+++ b/pandas/_libs/tslibs/np_datetime.pyx
@@ -1,4 +1,3 @@
-cimport cython
 from cpython.datetime cimport (
     PyDateTime_CheckExact,
     PyDateTime_DATE_GET_HOUR,
@@ -18,6 +17,7 @@ from cpython.object cimport (
     Py_LT,
     Py_NE,
 )
+from libc.stdint cimport INT64_MAX
 
 import_datetime()
 PandasDateTime_IMPORT
@@ -545,7 +545,6 @@ cdef ndarray astype_round_check(
     return iresult
 
 
-@cython.overflowcheck(True)
 cdef int64_t get_conversion_factor(
     NPY_DATETIMEUNIT from_unit,
     NPY_DATETIMEUNIT to_unit
@@ -553,6 +552,7 @@ cdef int64_t get_conversion_factor(
     """
     Find the factor by which we need to multiply to convert from from_unit to to_unit.
     """
+    cdef int64_t value, overflow_limit, factor
     if (
         from_unit == NPY_DATETIMEUNIT.NPY_FR_GENERIC
         or to_unit == NPY_DATETIMEUNIT.NPY_FR_GENERIC
@@ -565,28 +565,44 @@ cdef int64_t get_conversion_factor(
         return 1
 
     if from_unit == NPY_DATETIMEUNIT.NPY_FR_W:
-        return 7 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_D, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_D, to_unit)
+        factor = 7
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_D:
-        return 24 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_h, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_h, to_unit)
+        factor = 24
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_h:
-        return 60 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_m, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_m, to_unit)
+        factor = 60
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_m:
-        return 60 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_s, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_s, to_unit)
+        factor = 60
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_s:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ms, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ms, to_unit)
+        factor = 1000
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_ms:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_us, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_us, to_unit)
+        factor = 1000
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_us:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ns, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ns, to_unit)
+        factor = 1000
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_ns:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ps, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_ps, to_unit)
+        factor = 1000
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_ps:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_fs, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_fs, to_unit)
+        factor = 1000
     elif from_unit == NPY_DATETIMEUNIT.NPY_FR_fs:
-        return 1000 * get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_as, to_unit)
+        value = get_conversion_factor(NPY_DATETIMEUNIT.NPY_FR_as, to_unit)
+        factor = 1000
     else:
         raise ValueError("Converting from M or Y units is not supported.")
 
+    overflow_limit = INT64_MAX // factor
+    if value > overflow_limit or value < -overflow_limit:
+        raise OverflowError("result would overflow")
+
+    return factor * value
+
 
 cdef int64_t convert_reso(
     int64_t value,
@@ -595,7 +611,7 @@ cdef int64_t convert_reso(
     bint round_ok,
 ) except? -1:
     cdef:
-        int64_t res_value, mult, div, mod
+        int64_t res_value, mult, div, mod, overflow_limit
 
     if from_reso == to_reso:
         return value
@@ -624,9 +640,12 @@ cdef int64_t convert_reso(
     else:
         # e.g. ns -> us, risk of overflow, but no risk of lossy rounding
         mult = get_conversion_factor(from_reso, to_reso)
-        with cython.overflowcheck(True):
+        overflow_limit = INT64_MAX // mult
+        if value > overflow_limit or value < -overflow_limit:
             # Note: caller is responsible for re-raising as OutOfBoundsTimedelta
-            res_value = value * mult
+            raise OverflowError("result would overflow")
+
+        res_value = value * mult
 
     return res_value