Aim: Self-medication with antibiotics and antimalarials occurs among the population in Ethiopian. We studied to estimate the prevalence of self-medication with antibiotics and antimalarials in Ethiopia and evaluate factors associated with self-medication. Method: A cross-sectional study was conducted on 405 households, selected from Silte Zone in South Ethiopia, using a random sampling technique by employing a pretested questionnaire. Data were analyzed using SPSS for windows version 16.0. Chi-square test was used to observe the association of variables. Results: The prevalence of self-medication with antibiotics/antimalarias in this study was (14.5%). Twenty seven (6.7%) self medicated with antibiotics, 2.72% used antimalarial drugs while 21 (5.20%) used both. Level of monthly income and educational status significantly influence pattern of antibiotics and antimalarial self medication (P<0.05) The top three diseases that led to self medication in this study were headache (38.5%), fever (35.9%), and cough (14.1%). Among self-medicated antibiotics, Amoxicillin (13.5%) followed by Ciprofloxacin (8.5%) were the most commonly used class of drug. From antimalarial drugs chloroquine (10.1%) were highly abused. The main source of antibiotics /antimalarias was community pharmacies (58.97%) followed by shops (Kiosks) (17.95%). The majority (20.51%) of the respondents practiced self medication to avoid waiting time at health facilities. Conclusion: The Prevalence of self-medication with antibiotic/antimalaria in the study community was low. Self medication tended to be higher in people with a higher education and those on higher monthly incomes. The major reason for self-medication is found to be to avoid waiting time at health facility. Community pharmacies are the major source drugs.