Background Even if modern medicine is becoming more widely available, a considerable portion of the world’s population continues to rely on complementary and alternative medicine. Complementary and alternative medicine is used by 80% of the population in developing countries for their health care. The study was conducted to assess Knowledge, Attitude and practice towards complementary and alternative medicine and associated factors among health care professionals in public health facilities of Hadiya Zone, South Ethiopia. Methods The study was conducted in Hadiya Zone from October 10 to October 30, 2019. A facility-based cross-sectional study design was employed using simple random sampling methods. Three hundred sixty six health care professionals were selected using a simple random sample method. The data were collected using a standardized self-administered and pre-tested questionnaire that was adapted from different literatures. We used descriptive statistics, as well as bivariate and multivariate logistic regression analysis. An association was determined using P-values less than 0.05 and 95 percent confidence intervals. The results of the study were presented using texts and tables. Results Three hundred and fifty-five respondents were interviewed, with a 97 percent respondent rate. Two hundred thirty-two (65.4%) of the study participants have good knowledge towards complementary and alternative medicine, 216 (60.8%) have a favorable attitude toward complementary and alternative medicine, and 182 (51.3%) have utilized it in the previous two years. Some of the factors associated with knowledge, attitude, and practice towards complementary and alternative medicine were health care professionals who have contact with patients who seek complementary and alternative medicine [AOR = 1.89(95% CI; 1.18, 3.03), female health care professionals [AOR = 2.43(95% CI; 2.68, 9.74), and more than six years work experience [AOR = 1.68(95% CI; 1.04, 2.71). Conclusion The knowledge, attitude, and practice of complementary and alternative medicine among health care professionals were low. Creating communication lines with patients and facilitating the integration of complementary and alternative medicine with modern medicine.