Food-additive toxicity has become a major health hazard issue globally. Alloxan (ALX), a food-additive, intaken daily through flour causes diabetes and genotoxicity by inducing chromosomal-aberration and DNA-damage. The use of phytochemicals as a protective measure of health hazards has become quite evident because of their least side effects. Pelargonidin (PG), one such phyto-product, have an anti-genotoxic and anti-diabetic effect. In this study, the possibility of PG to inhibit alloxan-induced chromosomal-aberration and DNA-damage was assessed in mice model in vivo and the experimental outcome was validated theoretically through in silico structure-based molecular docking study. Results of the mitotic-index observed from the PG-pre-treated-alloxan-administered (PG+ALX) mice group revealed a significant reduction in chromosomal-anomaly, DNA-damage, and an upregulation of the p53 and PARP protein expression when compared to the ALX-treated mice group. Additionally, the in silico molecular docking study predicted the biochemical mechanism of actions of pelargonidin by identifying the two important amino acid residues p53 and PARP as the active bio-targets of pelargonidin. Therefore, results of our present in vivo and silico studies implicate that pelargonidin could effectively restrict DNA-damage and chromosomal-aberration by modulating PARP and p53 repair proteins showing its ability for possible protein-drug interaction, an effective therapeutic tool in future drug discovery.