Disinfection is intended to improve drinking water quality and human health. Although disinfectants may transform organic matter and form disinfection by-products (DBPs), many are branded as cyto- and genotoxic. Traditionally, research focuses on the effects of DBPs on human health, but cytogenic impacts on aquatic organisms still remain ill defined. The current study examines the potential toxic effect of chloroform and iodoform (DBPs) on Cyprinus carpio, selected as a model organism. Fish specimens were exposed to various concentrations of DBPs primarily based on LD50 values, where acute toxicity was monitored for 96 h. Headspace SPME extraction through gas chromatography was employed to assess the effects of spiked DBPs doses in fish blood. Cytotoxicity was monitored using Comet assay. Tail length, tail DNA, and olive tail moment values were quantified to be significant (P < 0.05) as compared to control. A statistically significant (P < 0.05) decrease in all blood parameters (hematology) was observed. Changes in biochemical indices (glucose, total protein, and alanine aminotransferase (ALT)) were also significant. ALT secretion was significantly increased (93 ± 0.05 and 82.8 ± 0.1 U/L) at higher concentration compared to control (56 ± 0.1 U/L), suggesting liver damage. Results demonstrated that iodoform was statistically more damaging as compared to chloroform.