Obesity is a major global health concern linked to cognitive impairment and neurological disorders. Circulating brain-derived neurotrophic factor (BDNF), a protein crucial for neuronal growth and survival, plays a vital role in brain function and plasticity. Notably, obese individuals tend to exhibit lower BDNF levels, potentially contributing to cognitive decline. Physical exercise offers health benefits, including improved circulating BDNF levels and cognitive function, but the specific impacts of acute versus regular exercise on circulating BDNF levels in obesity are unclear. Understanding this can guide interventions to enhance brain health and counter potential cognitive decline in obese individuals. Therefore, this study aimed to explore the impact of acute and regular physical exercise on circulating BDNF in individuals with obesity. The target population comprised individuals classified as overweight or obese, encompassing both acute and chronic protocols involving all training methods. A comprehensive search was conducted across computerized databases, including PubMed, Academic Search Complete, and Web of Science, in August 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Initially, 98 studies were identified, from which 16 studies, comprising 23 trials, met the selection criteria. Substantial heterogeneity was observed for both acute (I² = 80.4%) and long-term effects (I² = 88.7%), but low risk of bias for the included studies. A single session of exercise increased circulating BDNF levels among obese patients compared to the control group (ES = 1.25, 95% CI = 0.19 to 2.30, p = 0.021). However, with extended periods of physical exercise, there was no significant increase in circulating BDNF levels when compared to the control group (ES = 0.49, 95% CI = -0.08 to 1.06, p = 0.089). These findings highlight the need to consider exercise duration and type when studying neurobiological responses in obesity and exercise research. The study's results have implications for exercise prescription in obesity management and highlight the need for tailored interventions to optimize neurotrophic responses. Future research should focus on elucidating the adaptive mechanisms and exploring novel strategies to enhance BDNF modulation through exercise in this population. However, further research is needed considering limitations such as the potential age-related confounding effects due to diverse participant ages, lack of sex-specific analyses, and insufficient exploration of how specific exercise parameters (e.g., duration, intensity, type) impact circulating BDNF.