Background <p>Self-medication of antibiotics is a growing concern of modern world as misuse and overuse of antibiotics not only increase the risk of adverse side effects but also contribute to a higher rate of development of antimicrobial resistance. Studies have reported adverse effects of prolonged antibiotic use on health although there has been a constant debate about the potential risk of antibiotic consumption.</p> Objective <p>The present study was&#xa0;aim to investigate the genotoxicological effect of sub-chronic exposure to amoxicillin, azithromycin, and ciprofloxacin in bone marrow cells of albino mice. Animals (<i>n</i> = 40) were split into four groups, group I was negative control while groups II–IV were treated with amoxicillin, azithromycin, and ciprofloxacin respectively once a week for ten weeks.</p> Results <p>Exposure to antibiotics significantly increases the frequency of chromosomal aberration and micronuclei induction and reduces the percentages of mitotic index in bone marrow cells. Antibiotics treatment also caused significant DNA fragmentation in peripheral lymphocytes of the treated animals. Sub-chronic exposure to antibiotics induces oxidative stress by increasing the MDA level and reducing the GSH in the serum of treated animals, which also resulted in increased oxidative DNA damage as depicted by a significantly higher concentration of 8-OHdG.</p> Conclusion <p>The findings of the present study suggest that prolonged antibiotic exposure can potentially lead to significant cytotoxic, genotoxic, and clastogenic effects in mice by elevating oxidative stress levels.</p>