Social media is a powerful platform for disseminating health information, yet it is often riddled with misinformation. Further, few guidelines exist for producing reliable, peer-reviewed content. This study describes a framework for creating and disseminating evidence-based videos on polycystic ovary syndrome (PCOS) and thyroid conditions to improve health literacy and tackle misinformation. The study aims to evaluate the creation, dissemination, and impact of evidence-based, peer-reviewed short videos on PCOS and thyroid disorders across social media. It also explores the experiences of content creators and assesses audience engagement. This mixed methods prospective study was conducted between December 2022 and May 2023 and comprised five phases: (1) script generation, (2) video creation, (3) cross-platform publication, (4) process evaluation, and (5) impact evaluation. The SIMBA-CoMICs (Simulation via Instant Messaging for Bedside Application-Combined Medical Information Cines) initiative provides a structured process where medical concepts are simplified and converted to visually engaging videos. The initiative recruited medical students interested in making visually appealing and scientifically accurate videos for social media. The students were then guided to create video scripts based on frequently searched PCOS- and thyroid-related topics. Once experts confirmed the accuracy of the scripts, the medical students produced the videos. The videos were checked by clinical experts and experts with lived experience to ensure clarity and engagement. The SIMBA-CoMICs team then guided the students in editing these videos to fit platform requirements before posting them on TikTok, Instagram, YouTube, and Twitter. Engagement metrics were tracked over 2 months. Content creators were interviewed, and thematic analysis was performed to explore their experiences. The 20 videos received 718 likes, 120 shares, and 54,686 views across all platforms, with TikTok (19,458 views) and Twitter (19,678 views) being the most popular. Engagement increased significantly, with follower growth ranging from 5% on Twitter to 89% on TikTok. Thematic analysis of interviews with 8 out of 38 participants revealed 4 key themes: views on social media, advice for using social media, reasons for participating, and reflections on the project. Content creators highlighted the advantages of social media, such as large outreach (12 references), convenience (10 references), and accessibility to opportunities (7 references). Participants appreciated the nonrestrictive participation criteria, convenience (8 references), and the ability to record from home using prewritten scripts (6 references). Further recommendations to improve the content creation experience included awareness of audience demographics (9 references), sharing content on multiple platforms (5 references), and collaborating with organizations (3 references). This study demonstrates the effectiveness of the SIMBA CoMICs initiative in training medical students to create accurate medical information on PCOS and thyroid disorders for social media dissemination. The model offers a scalable solution to combat misinformation and improve health literacy.