Nurses have high work stress that may contribute to an increased overdose for sedatives, hypnotics, and antipsychotics (OSHA). We conducted this nationwide population-based cross-sectional study to clarify this still unclear issue. We used a nationwide database to identify 110,379 nurses, 22,032 other healthcare providers (HCPs), and an identical number of individuals from the general population matched by age and sex. We compared the period prevalence of OSHA between nurses and the general population, other HCPs and the general population, and nurses and other HCPs, among nurse subgroups from 2006 to 2012. The risk for OSHA in nurses and in the general population was not significantly different after adjusting for anxiety, insomnia, depression, schizophrenia, and affective disorders (adjusted odds ratio [AOR]: 1.145; 95% confidence interval [CI]: 0.974-1.346). However, in the age subgroups < 35 years, nurses had higher risk than the general population of having OSHA (AOR: 1.333; 95% CI: 1.109-1.601). Other HCPs had a significantly lower risk for OSHA than the general population (AOR: 0.237; 95% CI: 0.122-0.460). Nurses had a significantly higher risk for OSHA than other HCPs (AOR: 3.902; 95% CI: 2.159-7.048). Comparison among nurses showed that younger nurses (< 35 years) had a significantly higher risk for OSHA than the older nurses (≥ 50 years) (AOR: 3.569; 95% CI: 1.252-10.330). Registered nurses had significantly higher risk for OSHA than registered professional nurses (AOR: 1.810; 95% CI: 1.405-2.332); and nurses from clinics, local hospitals, and regional hospitals had significantly higher risk than nurses from medical centers. This study delineated that nurses had a nearly four-fold risk for OSHA when compared to other HCPs. Younger nurses, registered nurses, and nurses from clinics, local hospitals, and regional hospitals had higher risks for OSHA than their respective nurse controls; it suggests that more attention should be given to the occupational health of these populations.