Adverse drug reactions (ADRs) are a significant cause of illness and death, particularly in countries with limited healthcare resources. Among all drug categories, antimicrobials contribute the highest percentage (28%) of ADRs compared to other medications. Ofloxacin, an antimicrobial agent used to treat various bacterial infections, has an ADR incidence rate of 4.27%. Although this figure may seem small, the combination of ofloxacin with ornidazole for gastrointestinal infections in India contributes to a substantial burden of ADRs. However, research specifically focused on the adverse reactions of ofloxacin has been lacking in recent years. To address this research gap, the objective of this study was to systematically review the adverse drug reactions associated with ofloxacin in both human and animal studies. The authors conducted a comprehensive search of the PubMed and Cochrane Library databases, covering articles related to ofloxacin's adverse drug reactions published. A total of 42 relevant articles were identified and analyzed. The study findings suggest an increasing side effect profile for ofloxacin, indicating the need for cautious and prudent use of this antimicrobial agent. The review highlights the importance of understanding and monitoring the adverse effects associated with ofloxacin to ensure patient safety and promote appropriate prescribing practices. By bridging the research gap regarding the adverse drug reactions of ofloxacin, this article contributes to addressing the need for more comprehensive knowledge in this area. The study's conclusions emphasize the importance of judiciously using ofloxacin due to its increasing side effect profile. This information can guide healthcare providers in making informed decisions regarding the use of ofloxacin, ultimately improving patient care and medication safety.