Proton pump inhibitors (PPIs) are commonly prescribed for acid-related conditions like GERD and peptic ulcers, yet emerging research suggests they impact the gut microbiota, the diverse community of microorganisms in the gastrointestinal tract. This review consolidates current evidence on how PPIs affect gut microbiota composition and function. Studies indicate that PPI use alters gut microbiota diversity and composition, often leading to decreased microbial richness and shifts in specific bacterial taxa, such as increased potentially pathogenic bacteria like Enterococcus and Streptococcus, and decreased beneficial bacteria like Bifidobacterium and Lactobacillus. Long-term PPI use is associated with dysbiosis, a microbial imbalance linked to various gastrointestinal and systemic health issues. The mechanisms behind PPI-induced microbiota alterations are complex, involving direct effects on gastric pH, which influence bacterial survival and growth in the stomach and intestine. Additionally, PPIs may indirectly impact microbial ecology through changes in gastrointestinal motility, bile acid secretion, and nutrient availability. The clinical implications of PPI-induced gut microbiota changes are significant, with dysbiosis associated with conditions like Clostridium difficile infection, SIBO, and IBD. Altered gut microbiota may also affect systemic health, including immune function, metabolism, and antibiotic resistance. In conclusion, while PPIs are effective in managing acid-related disorders, their influence on gut microbiota warrants consideration. Further research is necessary to understand the mechanisms underlying PPI-induced dysbiosis and develop strategies to mitigate adverse microbiota-related effects of long-term PPI use. Clinicians should be mindful of the potential impact on gut microbiota when prescribing PPIs and advocate for microbiota-friendly approaches to acid suppression therapy.