Doxorubicin (DOX) is a potent chemotherapeutic drug used in cancer treatment, but it can lead to neurotoxicity particularly in the peripheral nervous system causing neuropathic pain. Roselle extract, known for its neuroprotective properties, has gained attention as a potential therapeutic agent in mitigating such neurotoxic effects. In this study investigated the neuroprotective potential of roselle water extract (RWE) against DOX-induced neurotoxicity in rats, focusing on the spinal cord, sciatic nerve, and neuropathic pain. Male albino rats were divided into four groups (6 rats/group); control, RWE-treated (500 mg/kg body weight/day; oral adminstration), DOX-treated (cumulative dose of 18 mg/kg body weight; intraperitoneal injected), and DOX + RWE-treated groups. Various assessments, including thermal nociception tests (hot plate, tail flicking, and cold plate), biochemical analysis of oxidative stress markers including malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and histopathological evaluation of spinal cord and sciatic nerve tissues were conducted. DOX treatment led to increases in oxidative stress (↑MDA, ↑MPO, ↓SOD, and ↓CAT), neuronal damage, axonal demyelination, astrocytes number, and microglial cell activation, and a reduction in Schwann cell population. However, concurrent administration of RWE with DOX significantly reduced oxidative stress, preserved neuronal morphology, decreased glial cells activation, improved Schwann cell density, and attenuated neuropathic pain responses compared to the DOX-only treated rats. These findings suggested that RWE possessed antioxidant and neuroprotective properties, making it a potential complementary therapy to alleviate peripheral neuropathy associated with DOX treatment.