Background and Objectives: Meditation and mindfulness, rooted in ancient traditions, enhance mental well-being by cultivating awareness and emotional control. It has been shown to induce neuroplasticity, increase cortical thickness, reduce amygdala reactivity, and improve brain connectivity and neurotransmitter levels, leading to improved emotional regulation, cognitive function, and stress resilience. This systematic review will synthesize research on neurobiological changes associated with mindfulness and meditation practices. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases without any search time range. This review has been registered on Open OSF (n) GV2JY. Results: Mindfulness-Based Stress Reduction (MBSR) enhances brain regions related to emotional processing and sensory perception, improves psychological outcomes like anxiety and depression, and exhibits unique mechanisms of pain reduction compared to placebo. Conclusions: This review highlights that mindfulness, particularly through MBSR, improves emotional regulation and brain structure, reduces anxiety, and enhances stress resilience. Future research should focus on diverse populations and naturalistic settings to better understand and optimize these benefits.