Background: Oral isotretinoin is an effective treatment for refractory and moderate acne unresponsive to conventional therapies, considered the most effective option for such cases. Objective: This study aimed to evaluate the knowledge, concerns, and experiences of acne patients undergoing isotretinoin treatment in Qassim, Saudi Arabia, with a focus on commonly reported adverse effects. Methods: A cross-sectional study was conducted from December 2023 to February 2024 using a self-administered questionnaire. This study targeted male and female acne vulgaris patients from the Qassim region attending the outpatient dermatology clinic at King Saud Hospital (KSH). Results: A total of 131 acne patients participated. Of these, 97.7% had heard of isotretinoin, and 92.4% were aware of its side effects. The most common sources of information were colleagues, friends, or family (37.4%), followed by previous use (26%) and healthcare professionals (24%). The most frequently reported side effect was dryness (51.9%), followed by liver function changes (24.4%) and fetal abnormalities (13%). There was a significant association between educational level and knowledge of isotretinoin’s side effects (p = 0.003) and awareness of specific side effects (p < 0.001). Conclusion: Most acne patients had sufficient knowledge of isotretinoin and its adverse effects, with dryness being the most commonly reported side effect. The primary sources of information were non-medical, highlighting the need for health education to ensure informed and safe isotretinoin use.