Background: Complementary and Alternative Medicine (CAM) therapies include natural products and body and mind practices. According to WHO, up to 80% of developing country populations rely on CAM for their primary health care, due to cultural tradition and lack of alternatives. In KSA, 68% of the population used at least one time in the past twelve months. The Holy Quran is the most used CAM therapy (50.3%). Aim: The study aims to assess the knowledge, utilization, and attitude toward the use of CAM and to compare PHC physicians working in urban and rural areas of the Riyadh region. Method: Facility-based cross-sectional survey was conducted among physicians working in the PHC of urban and rural areas of the Riyadh region utilizing multistage stratified random sampling. Result: 230 physicians participated in the study, among them 55.7% and 44.3% of the physicians work in urban and rural areas of the Riyadh region, respectively. The majority of the physicians are male 61.7%, the age category of 25-35 (43.5%), Non-Saudi Arabian nationals 64.8%, GPs 64.3%, 1-5 years of work experience 47.4% and other than family medicine specialists 70%. 14.3% of the study participants mentioned that they participated in the lectures or workshops, or received training in the use of CAM. Honey and bee products 114 (49.6%) are the only CAM therapy; the majority of the physicians mentioned “understand and feel comfortable about counseling patients”. Regarding CAM products, the majority of physicians feel comfortable about counseling patients. There were a significantly higher understanding and feeling comfortable about counseling patients about CAM products among physician working inside Riyadh (p-value ≤ 0.001). 32.2% of the physicians mentioned that they never used CAM for themselves or the family. 93.9% of the physicians did not refer any patient to the CAM practitioner, and the majority are physicians working in urban Riyadh. The knowledge score is about 22.74 (SD=8.03), and the mean attitude score is about 6.13 (SD=2.67), and there is no significant difference between the physicians working inside and outside Riyadh. Conclusion: Overall, the physicians had adequate knowledge about the CAM products and low-level knowledge about the CAM therapies, and attitude was higher among physicians. The least number of physicians refers the patients to the CAM practitioner or initiate a discussion with the patients.