Traditionally, Diospyros lotus Linn is used for insomnia and other associated disorders. Insomnia is a worldwide disorder with different etiology which is treated with different synthetic medicine associated with addiction. Natural products are generally devoid of such addition with good efficacy. Current research was conducted to evaluate the sedative and hypnotic effects of dimeric naphthoquinones such as dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5) and dinaphthodiospyrol F (6) isolated from the chloroform fractions of D. lotus. The sedative and hypnotic effects at the dose of 5 and 10 mg/kg (each compound) were assessed through open field and phenobarbital induced sleep test, respectively. In the case of open field test the administration of tested compounds significantly hindered the movement of animals, while in case of hypnotic effect the tested samples significantly improved the onset and duration of sleep as compared to control. The overall effects were in a dose dependent manner. The compounds were also assessed for acute toxicity, but no toxicity was observed. In this regard, our research triumphantly announced the strong chemical base for the folkloric values of the plant with their fringe benefits and implemented a platform for further aspects of mechanistic and clinical studies. A possible mechanism of in vivo inhibition was studied by using docking simulations on GABA receptors. Binding orientations and types of interactions revealed that a possible mechanism behind these pharmacological actions might be interaction with GABA receptors. Display omitted •Six naphthoquinones; dinaphthodiospyrol (A-F) were isolated from the chloroform fractions of Diospyros lotus.•The dinaphthodiospyrol (A-F) showed excellent sedative effect at the dose of 20 mg/kg.•The dinaphthodiospyrol (A-F) showed significant hypnotic effect at the dose of 20 mg/kg.•Binding orientations and binding energy values show strong binding affinity of compounds with GABA receptors.