Purpose Handedness has been linked to various physiological and pathological phenomena including memory function and psychiatric disorders. Also for sleep, several studies have reported associations. However, large-scale studies including a broad age span of participants and studies analyzing women and men separately are lacking. Methods Therefore, objective sleep data were determined using at-home actigraphy from 1764 healthy participants (18 to 80 years, 908 women), averaging five consecutive nights. In addition, subjective sleep-related data were captured by self-report diaries, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the Morningness-Eveningness-Questionnaire (MEQ). Handedness was determined with the Edinburgh Handedness Inventory (EHI) providing information on the direction (left vs right) and the degree of handedness (strong vs weak). To address the potential endocrine effects, premenopausal women (≤45 years) and postmenopausal women (≥55 years) were analyzed separately. This was also done for men. Results The degree and direction of handedness were correlated with “wake after sleep onset” (WASO) in the total sample and all women (the more right-handed/lateralized the shorter WASO). In postmenopausal women, additionally, time in bed (TIB) and total sleep time (TST) were correlated. There were no other significant associations between an objective sleep variable and handedness. In both premenopausal women and >55-year-old men subjective quality of sleep (PSQI) was correlated with direction and degree of handedness (the more right-handed/lateralized the better). In the total sample and postmenopausal women, the degree and direction of handedness were negatively correlated with daytime sleepiness. The chronotype was not associated with handedness in any group. Conclusion While associations were not consistent in all groups, overall, right-handedness tended to be associated with better sleep and less daytime sleepiness. Handedness and sleep seemed to be differentially associated in women and men, being in line with endocrine interactions.