A new starch derivative with antibacterial properties and non‐hemolytic effect was synthesized through the chemical grafting of 4‐chloroaniline onto the backbone of potato starch. In a first step, starch was extracted from potatoes grown in the region of Coahuila, Mexico, using the water steeping method. The hydroxyl groups (C5‐C6) of the native starch were oxidized using sodium periodate. The resulting dialdehyde was then chemically modified through a Schiff base reaction with 4‐chloroaniline. The chemical structure of this starch derivative was confirmed by Fourier transform infrared and 1H NMR spectroscopies, the thermal properties were analyzed by thermogravimetric analysis without finding significant changes and the product showed antibacterial activity against Gram‐negative E. coli and Gram‐positive S. aureus strains. Finally, the hemolytic and cytotoxic effects of native starch and its derivative were studied, showing no hemolytic effect on isolated human red blood cells and no cytotoxic effect; therefore, it can be considered biocompatible. © 2024 Society of Chemical Industry.