diff --git a/mypy/types.py b/mypy/types.py
@@ -2941,7 +2941,15 @@ def slice(
             total = len(self.items)
             unpack_index = find_unpack_in_list(self.items)
             assert unpack_index is not None
-            if begin is None and end is None:
+            if (
+                begin is not None
+                and end is not None
+                and (begin >= 0) == (end >= 0)
+                and (begin >= end if stride is None or stride > 0 else begin <= end)
+            ):
+                # Start and end count from the same side, so the slice is empty for any length.
+                slice_items = []
+            elif begin is None and end is None:
                 # We special-case this to support reversing variadic tuples.
                 # General support for slicing is tricky, so we handle only simple cases.
                 if stride == -1:

diff --git a/test-data/unit/check-typevar-tuple.test b/test-data/unit/check-typevar-tuple.test
@@ -1587,6 +1587,21 @@ bt = t[::0]  # E: Slice step cannot be zero
 reveal_type(bt)  # N: Revealed type is "builtins.tuple[Any, ...]"
 [builtins fixtures/tuple.pyi]
 
+[case testVariadicTupleEmptySlice]
+from typing import Unpack, TypeVarTuple
+
+Ts = TypeVarTuple("Ts")
+def f(x: tuple[int, Unpack[Ts], str], y: tuple[int, Unpack[tuple[str, ...]]]) -> None:
+    reveal_type(x[2:1])  # N: Revealed type is "tuple[()]"
+    reveal_type(x[3:3])  # N: Revealed type is "tuple[()]"
+    reveal_type(x[-1:-2])  # N: Revealed type is "tuple[()]"
+    reveal_type(x[1:2:-1])  # N: Revealed type is "tuple[()]"
+    reveal_type(y[5:2])  # N: Revealed type is "tuple[()]"
+    reveal_type(y[-3:-3:2])  # N: Revealed type is "tuple[()]"
+    y[1:5]  # E: Ambiguous slice of a variadic tuple
+    y[-2:-5:-1]  # E: Ambiguous slice of a variadic tuple
+[builtins fixtures/tuple.pyi]
+
 [case testAnyVariadicTupleLenientUnpacking]
 from typing import Any, Unpack