Ciprofloxacin drugs are a second‐generation fluoroquinolone highly prescribed medication against various bacterial infections in human and aquaculture practices. These drugs are chemically designed to persist in the body long enough to achieve target objectives. Extensive usage has resulted in ciprofloxacin becoming a ubiquitous contaminant in the environment. Unfortunately, the ecotoxicological profiles for ciprofloxacin are scanty. This study was aimed to assess the ecotoxicity of ciprofloxacin at environmentally relevant concentrations (1 μg/L, and 1.5 μg/L) to a cultivable fish Cirrhinus mrigala. Responses of antioxidant enzymes, histological anomalies, and inorganic ion levels were studied. SOD activity in gill, liver, and kidney tissues was elevated in ciprofloxacin‐exposed groups when compared with the control group. CAT activity was predominantly decreased in ciprofloxacin treated groups relative to the control group. GST activity in the ciprofloxacin treated groups was increased (except kidney tissues [Treatment I (1 μg/L)], and gill tissues fifteenth day) significantly (p < .05). The LPO level was elevated in the ciprofloxacin treatment groups throughout the study period (except Treatment II (1.5 μg/L) tenth day in kidney tissues). A series of histological anomalies were noticed in the gill, liver, and kidney tissues of the ciprofloxacin treated groups. Ciprofloxacin exposure caused a significant decrease of sodium, potassium, and chloride levels in the plasma of C. mrigala. A parallel among an imbalanced oxidative defense system, tissue structural changes, and alterations of plasma inorganic ions could be considered as a reliable biomarker for antibiotic toxicity study. This study could be a primary platform for further toxicity studies to understand the potential molecular impacts and adverse effects of ciprofloxacin on aquatic organisms.