The interference in the metabolism of a drug by another drug, food or other foreign chemical is commonly observed and often leads to clinically significant adverse drug reactions. In Jamaica, there is an extensive use of natural products as medicines, although there is little information on whether natural medicines are used along with prescription medicines, which might increase the likelihood of drug adversities. This current pilot survey was initiated to gain information on the prevalence of such polypharmacy practices. Two concurrent surveys were carried out in Kingston (an urban parish) and Clarendon (a rural parish) in 743 patients above age 14 years with diabetes mellitus, hypertension and gastrointestinal disorders of persons who visited health centres and pharmacies. Patrons visiting these places at various times of the day were informed of the nature of the questionnaire and willing participants with the above disease conditions and who were on prescription medicines were included in the survey. The results indicated that 80% of the respondents reported combining natural products in their treatment along with prescription medicines, with only 13% of those patients informing their physicians of such practices. Such polypharmacy practices were independent of the type of disease among both males and females and was statistically most prevalent (p < 0.001) in the 47-57-year age group. There was a significant association (p < 0.001) between such treatment practices and place of residence with 92% of the rural community engaging in polypharmacy but 70% of the urban did likewise. Therefore, being aware of the prevalence of multiple therapy practices would be especially useful when designing a pharmaco-vigilance system.