Background Self-medication is the use of any drug or medication to treat an illness or ailment without the supervision of a licensed medical doctor/health care providers. Self-medication practice in Eastern Ethiopia is quite common. However, there is little information with regard to magnitude and associated factors. The objective of this study was to assess the magnitude of self-medication practice and associated factors among adult community members of Jigjiga town, Eastern Ethiopia. Methods A community based cross-sectional study was conducted from June 27- July 12, 2017. Multistage sampling method was used and the number of kebeles and Sub-kebeles were selected using simple random sampling technique. Finally, sampled households in the Sub-kebeles were selected using systematic random sampling. Data were collected using face to face interview with 547 adult (≥18 years) participants. It was entered and cleaned using EPI-Data version 3.02 and exported to Statistical Package for Social Science (SPSS) Version 23 for further analysis. Bi-variable and multivariable logistic regression models were carried out to identify factors associated with the self-medication. Result The magnitude of self-medication was found to be 37.5% (95% CI: (33.6%–41.7%). Educational status of secondary school [(AOR = 0.46; 95% CI: (0.22–0.98)], high income [(AOR = 3.00; 95% CI: (1.77–5.06)], advised by neighbors, friends or relatives to take drug for their complaint [(AOR = 2.59; 95% CI: (1.62–4.14)], used old prescription /past experience to bought drugs [(AOR = 12.19; 95% CI: (6.65–22.35)], follow advertisements of drugs by television [(AOR = 0.21; 95% CI: (0.05–0.85)], and perception about Hospital drugs (clinics, health centers and hospitals) do not work [(AOR = 2.36; 95% CI: (1.39–3.99)] were significantly associated with self-medication. Conclusion High income, advice by neighbors, friends or relatives to take drug for their complaint, old prescription/past experience use to bought drugs, and perception of hospital drugs do not work was positively associated with self-medication. Therefore, health education should be given to the community on the importance of hospital drugs (clinics, health centers and hospitals) to shift their perception.