Fluoroquinolones (FQs) are widely prescribed antibiotics; however, increasing concerns have arisen over their potential to cause disabling and irreversible adverse effects. Using real-world data from the FDA Adverse Event Reporting System (FAERS) (2011–2024), we performed disproportionality analyses on psychiatric and eye-related adverse events (AEs) using reporting odds ratios (RORs). Of 44 895 FQ-associated adverse event reports, 8518 cases exhibited psychiatric AEs whilst 4367 cases displayed eye-related AEs. Among six FDA-approved FQs, three (ciprofloxacin/levofloxacin/moxifloxacin) showed safety signals for psychiatric disorders and four (ciprofloxacin/levofloxacin/moxifloxacin/ofloxacin) for eye-related disorders. Eight psychiatric and nine eye-related AEs were commonly reported across multiple FQs. Importantly, moxifloxacin exhibited unique safety signals for ocular-related toxicity, including iris transillumination defect [ROR: 6604.89 (4736.76–9209.81)], iris hypopigmentation [1887.66 (1175.44–3031.42)], and pigment dispersion syndrome [2360.62 (1432.71–3889.51)], raising concern for potential progression to pigmentary glaucoma—findings not prominently featured in current safety warnings. Additionally, systematic characterization of suicide cases revealed striking male predominance despite females comprising the majority of psychiatric AEs, identifying middle-aged males as a high-risk demographic. These findings support the need for enhanced pharmacovigilance, particularly regarding moxifloxacin's ocular toxicity and FQs' suicide vulnerability in specific patient subgroups. When FQ prescription becomes unavoidable, robust safety monitoring should be implemented to detect early neuropsychiatric and ocular complications.