Objective: The aim of this hospital-based, cross-sectional study was to examine nurses' knowledge, personal and professional practices and attitude towards complementary and alternative medical therapies in urban Ghana. Method: Using convenience sampling technique, cross-sectional data were collected from 210 registered and practicing nurses with self-administered questionnaire based on the Complementary and Alternative Medicine (CAM) Health Belief Questionnaire (CHBQ). Descriptive statistics and the associations between variables were calculated using Pearson's Chi-square test and/or Fisher's exact test with p < 0.05. Results: The mean score of nurses' knowledge on CAM therapies was low (mean ± SD, 38.39 ± 10.11; possible range, 18–72) which was built on nurses' personal experiences. Nurses, therefore, lacked the confidence to recommend CAM therapies to patients. Despite the isolated cases of non-herbal supplements, relaxation techniques, massage and prayer healing, the study found an overall low personal use of CAM (mean ± SD, 32.97 ± 10.78; possible range, 18–72) among nurses over the last 12 months. Yet, nurses exhibited a positive attitude towards CAM (mean ± SD, 72.7 ± 12.5, possible range, 67–110). We observed significant associations among nurses' CAM knowledge and education [χ2 (2) = 6.69, p = 0.035] and religion [χ2 (2) = 7.96, p = 0.019]; nurses' personal use of CAM and income [χ2 (2) = 16.07, p < 0.001] and religion [χ2 (2) = 18.65, p < 0.001]; and nurses' clinical CAM use and income [χ2 (2) = 7.01, p = 0.030]. Conclusion: Despite the overall positive attitude towards CAM therapies, Ghanaian nurses do not perceive themselves to have sufficient knowledge of CAM. Integrating CAM education into the nurses' training curriculum can improve CAM knowledge and professional practice among nurses, and in turn, enhance evidence-based patient care within the framework of intercultural healthcare system in Ghana.