Fibromyalgia syndrome (FMS) is a chronic, multidimensional musculoskeletal condition distinguished by severe nociceptive dysfunction, persistent fatigue, sleep disruptions, cognitive deficits, and emotional instability. Although valproic acid (VPA) has been used to treat epilepsy and bipolar disorder, its efficacy in altering neuropathic pain pathways remains unclear. In this investigation, we assessed the neuromodulatory characteristics of VPA (300 mg/kg, intraperitoneally) in an established FMS rat model, with a focus on neuroinflammation, oxidative stress, and glial activation. Behavioral evaluations for thermal hyperalgesia (paw withdrawal latency, PWL) and mechanical allodynia (paw withdrawal threshold, PWT) were performed at baseline (day 0), after induction (day 5), and at various intervals following VPA administration. Neurochemical evaluations demonstrated that VPA markedly diminished FMS-induced elevations in malondialdehyde (MDA), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and interleukin (IL)-6, while restoring antioxidant defenses, such as glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination demonstrated reduced neuronal degeneration and decreased immunoreactivity of glial fibrillary acidic protein (GFAP). These findings indicate that VPA reduces FMS-related pain and neuroinflammatory characteristics through antioxidative and glial-modulating mechanisms, indicating its potential for therapeutic repurposing in neuropathic pain syndromes.