Background: Cognitive impairment is prevalent in disorders and aging, and is worsened by oxidative stress, neuroinflammation, and cholinergic dysfunction. Aluminum chloride (AlCl₃)-induced neurotoxicity models exhibit cognitive deficits and Alzheimer's disease-like pathology. Adenium obesum and Coenzyme Q10 (CoQ10) may provide neuroprotective benefits. Objective: This study aimed to investigate the neuroprotective effects of Adenium obesum and CoQ10, administered individually and in combination, against AlCl₃-induced cognitive impairment in rats. This study also evaluated the potential of Nanostructured Lipid Vesicles (NLVs) to enhance the bioavailability and brain delivery of these therapeutic agents. Methods: Cognitive impairment was induced in rats using aluminum chloride (AlCl₃). Thereafter, the rats in the treatment groups were treated with nanostructured lipid formulations in suitable dose (160 mg/kg body weight) of adenium obesum extract and CoQ10 (1.5 mg/kg body weight). Behavioral assessments, including the Morris Water Maze (MWM) and Elevated Plus Maze (EPM), were performed to evaluate learning and memory functions. Biochemical analyses were conducted to determine the acetylcholinesterase (AChE) activity, oxidative stress markers, and antioxidant enzyme levels. The NLC formulation was developed to improve stability, bioavailability, and targeted brain delivery of therapeutic compounds. Results: Treatment with adenium obesum extract and CoQ10 significantly improved cognitive performance and attenuated AlCl₃-induced memory deficits in rats compared to the disease control group. The combination therapy delivered through NLVs exhibited superior neuroprotective activity, as evidenced by enhanced behavioral outcomes, reduced acetylcholinesterase (AChE) activity, decreased oxidative stress, and improved antioxidant defense mechanisms. Furthermore, the NLV-based formulation improved drug delivery efficiency, contributing to enhanced therapeutic efficacy.