Probiotics, defined as live microorganisms that confer health benefits on the host when administered in adequate amounts, have emerged as a vital component in promoting and maintaining human health through modulation of the gut microbiota and beyond. This systematic review aims to synthesize current evidence on the multifaceted role of probiotics in improving gastrointestinal health, enhancing immune responses, mitigating metabolic disorders, and influencing mental well-being via the gut-brain axis. An extensive literature search was conducted across major databases, including PubMed, Scopus, and Web of Science, encompassing peer-reviewed randomized controlled trials, cohort studies, and systematic reviews published between 2010 and 2024. The selected studies consistently demonstrate that probiotics, particularly strains of Lactobacillus and Bifidobacterium, can effectively reduce the incidence of antibiotic-associated diarrhea, inflammatory bowel conditions, and respiratory infections, while also improving insulin sensitivity, lowering blood pressure, and reducing systemic inflammation. Moreover, emerging research highlights the potential of probiotics as psychobiotics—modulating stress, anxiety, and depressive symptoms through their influence on neurotransmitter pathways and immune regulation. However, variability in clinical outcomes remains a challenge, often attributed to strain-specific differences, inconsistent dosing, and host-related factors. While generally considered safe, probiotics may pose risks in immunocompromised populations, emphasizing the need for targeted administration and robust safety assessments. This review underscores the promise of probiotics as a safe, non-invasive adjunct to conventional medicine, while calling for standardized clinical protocols, personalized approaches, and global regulatory oversight to ensure efficacy, safety, and public confidence in probiotic therapies.