In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4‐(alkylamino)‐3‐nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec‐butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg–1, were evaluated in light/dark, open‐field, horizontal wire and diazepam‐induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic‐like effect. 4‐(sec‐Butylamino)‐3‐nitro‐2H‐chromen‐2‐one and 4‐(hexadecylamino)‐3‐nitro‐2H‐chromen‐2‐one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3‐nitrocoumarin core deserves further chemical diversity exploration in the ‘antianxiety’ direction.