Background Patients with persistent physical symptoms presenting in primary care are often affected by multiple symptoms and reduced functioning. The medical and societal costs of these patients are high, and there is a need for new interventions tailored to both the patients and health care system. Objective This study aimed to examine the usability of an unguided, self-help treatment program, “My Symptoms,” developed to assist patients and general practitioners in symptom management. Methods In all, 11 users (4 patients with persistent physical symptoms and 7 laypeople) participated in web-based thinking-aloud interviews involving the performance of predefined tasks in the program. Thematic analysis was used to categorize the severity of usability issues. General usability heuristics were cross-referenced with the usability issues. Results The analysis identified important usability issues related to functionality, navigation, and content. The study shows how therapeutic knowledge in some cases was lost in the translation of face-to-face therapy to a digital format. The user testing helped uncover how the functionality of the digital elements and general navigation of the program played a huge part in locating and accessing the needed treatment. Examples of redesign to mediate the therapeutic value in the digital format involving health care professionals, web developers, and users are provided. The study also highlights the differences of involving patients and laypeople in the interviews. Conclusions Taking the experience of common symptoms as a point of departure, patients and laypeople contributed to finding usability issues on program functionality, navigation, and content to improve the program and make the treatment more accessible to users.