Background <p>Cannabidiol (CBD) has emerged as a promising neuroprotective compound, with potential benefits for cognitive and emotional behaviors. However, the consistency of its effects across preclinical models remains uncertain.</p> Methods <p>We conducted a systematic review and meta-analysis of 123 animal studies assessing the impact of CBD on anxiety-like and depressive-like behaviors, as well as cognition.</p> Results <p>CBD consistently reduced anxiety- and depressive-like behaviors, with moderate effect sizes observed in paradigms such as the elevated plus maze, novelty suppressed feeding, forced swim, sucrose preference, and tail suspension test. Cognitive effects were more heterogeneous: CBD improved performance in adverse, discriminatory, and working memory tasks, while effects were small or inconsistent in hippocampus-dependent spatial memory tests. Subgroup analyses revealed that CBD’s efficacy often depended on the type of behavioral test and the presence of underlying pathologies. Mechanistic evidence implicates serotonergic signaling (notably 5-HT1A receptors), endocannabinoid modulation, anti-inflammatory and neurotrophic pathways, as well as mitochondrial and synaptic plasticity processes, as contributors to these behavioral outcomes. Risk of bias assessment indicated moderate to high quality across studies, confirming the robustness of the findings.</p> Conclusions <p>Overall, our results indicate that CBD reduces anxiety-like and depressive-like behaviors and improves cognitive performance across a variety of preclinical models. While these findings support its therapeutic potential and provide a rationale for guiding translational research, clinical evidence in humans is still limited and inconclusive, underscoring the need for further research.</p>