Khat chewing is commonplace in Yemen, but little else is known about the misuse of other drugs, especially how such misuse may intersect with Khat use. The aim of this study was to investigate misuse of prescription and over-the-counter (OTC) drugs in community pharmacies in Aden city, from the users’ perspective. A qualitative in-depth-interview study was undertaken with fifteen known or suspected drug misusers, recruited through community pharmacies. Thematic analysis was used to identify the main emergent themes around experience of prescription and OTC drug misuse. The majority of interviewees were male (n = 11/15) with an age range of 21–40 years. Benzodiazepines, Tramadol, and Ketoprofen were the most commonly misused drugs. Four main themes were identified: Experience sought with drugs; awareness of problematic drug use; pattern and methods of misuse; and the role of healthcare professionals in responding to misuse. The study highlighted different issues, such as the practice of mixing different OTC and prescription drugs with Khat to heighten the effects or manage associated pain, and drug misuse by females and by health care professionals. The study also suggested that physicians and pharmacists fear counselling such people, probably with the risk of violence as a contributory factor.