Brain-Derived Neurotrophic Factor (BDNF) is crucial for various aspects of neuronal development and function, including synaptic plasticity, neurotransmitter release, and supporting neuronal differentiation, growth, and survival. It is involved in the formation and preservation of dopaminergic, serotonergic, GABAergic, and cholinergic neurons, facilitating efficient stimulus transmission within the synaptic system and contributing to learning, memory, and overall cognition. Furthermore, BDNF demonstrates involvement in neuroinflammation and showcases neuroprotective effects. In contrast, BDNF antisense RNA (BDNF-AS) is linked to the regulation and control of BDNF, facilitating its suppression and contributing to neurotoxicity, apoptosis, and decreased cell viability. This review article aims to comprehensively overview the significance of single nucleotide polymorphisms (SNPs) in BDNF/BDNF-AS genes within psychiatric conditions, with a specific focus on their associations with depression, schizophrenia, and bipolar disorder. The independent influence of each BDNF/BDNF-AS gene variation, as well as the interplay between SNPs and their linkage disequilibrium, environmental factors, including early-life experiences, and interactions with other genes, lead to alterations in brain architecture and function, shaping vulnerability to mental health disorders. The potential translational applications of BDNF/BDNF-AS polymorphism knowledge can revolutionize personalized medicine, predict disease susceptibility, treatment outcomes, and guide the selection of interventions tailored to individual patients.