Background <p>Aluminum is recognized for its toxicity in humans and animals. This study investigates the protective effects of <i>Spondias mombin</i> leaf extracts against oxidative stress, inflammation, and apoptosis in male Wistar rats. Rats were divided into nine groups, receiving 100&#xa0;mg/kg AlCl₃ for 3 weeks, followed by a 2-week treatment with <i>Spondias mombin</i> leaf extract (SME) or its fraction (SMF) at 100 and 200&#xa0;mg/kg. Brain tissues were analyzed using biochemical, molecular, and histopathological techniques.</p> Results <p>Phytochemical analysis confirmed the presence of tannins, phenols, terpenoids, flavonoids and steroids, while HPLC analysis identified kaempferol and other polyphenols, in the <i>Spondias mombin</i> extracts. Aluminum exposure led to increased oxidative and inflammatory damage in brain tissue as revealed by decreased glutathione concentrations and antioxidant enzyme activities, along with elevated levels of tumor necrosis factor-alpha, nitric oxide, myeloperoxidase, xanthine oxidase, and lactate dehydrogenase. Caspase-3, and BCL2 associated X (Bax) levels were also increased in AlCl₃-exposed rats. Both SME and SMF mitigated AlCl₃-induced redox imbalance, proinflammatory events, and neuronal cell death by enhancing levels of reduced glutathione and antioxidant enzyme activities, reducing the levels of inflammatory biomarkers, and preserving hippocampal formation and neuronal cell organization.</p> Conclusions <p>These findings highlight the therapeutic potential of <i>Spondias mombin</i> leaf extracts against aluminum-induced neurotoxic effects through their antioxidant, anti-inflammatory, and antiapoptotic properties.</p> Graphical abstract <p></p>