Background: Depression and other stress-related mental disorders are the leading causes of disability worldwide, making them a significant global health challenge. This systematic review aimed to determine the effects of psychobiotic microorganisms on mental health outcomes, with particular focus on their sources, metabolites, and therapeutic potential for depression. Methods: A systematic review following PRISMA guidelines was conducted using publications from 2020 to 2024 in Web of Science, Scopus, and PubMed databases. Inclusion criteria encompassed studies examining psychobiotics and their effects on mental health in humans and experimental animals. Risk of bias assessment was performed using the Cochrane Risk of Bias Tool (ROB 2). Results: Of 369 identified articles, 45 met inclusion criteria. The predominant psychobiotic strains belonged to Lactobacillus (45.5%) and Bifidobacterium (29%) genera. Strain sources included commercial preparations (24%), human-derived (16%), and food-derived (16%) strains. Psychobiotic bacterial strains produce neuromodulatory metabolites, such as short-chain fatty acids (SCFAs), neurotransmitters (e.g., GABA and serotonin), and indole derivatives that influence the gut–brain axis. Their mechanisms of action include neurotransmitter regulation (27.1%), modulation of the gut microbiota (27.1%), SCFA production (16.9%), and control of inflammatory responses (15.3%). Lactobacillus plantarum, Bifidobacterium breve, and Akkermansia muciniphila demonstrated particularly promising effects. Conclusions: Psychobiotics show significant potential as adjunctive and therapeutic agents in depressive disorders through modulation of the gut–brain axis.