Background: A comparative study of classical medical texts within Traditional Medicine provides a vital framework for uncovering the origins, development, transmission, and historical significance of healing traditions. This approach highlights a specific culture’s contribution to medical knowledge and reflects the intricate interplay of religion, culture, and philosophical thought embedded in those eras. Aim: To conduct a comparative analysis of the depictions of the “Medicinal Mandala” as described in the first chapter of the “Root Tantra” section in the two classical medical sources Sorig Bumshi and Gyudshi. Materials and Methods: This research examines two foundational Tibetan medical texts—Sorig Bumshi and Gyudshi—using theme-based classification and content analysis methodologies grounded in textual source criticism. Results: The findings confirm that Sorig Bumshi, a Bönpo medical text from the ancient Zhangzhung civilization, was composed earlier. The great translator Byaruzana translated it from the Zhangzhung language, after which Yuthok Yönten Gönpo and collaborators edited, revised, and systematized the text to form Gyudshi, embedding it in Buddhist epistemological frameworks. Conclusions 1. The medicinal mandala of Gyudshi—structured around a central "beautiful medicinal city" surrounded by four directional mountains—demonstrates a refined adaptation of the more expansive, sacred mandala depicted in Sorig Bumshi, which is centered on Olmo Lung Ring, a Bönpo pure land rich in symbolic geography. 2. The numerical values recorded in both texts—particularly the recurring use of 360 and 404—suggest different paradigms in medical theory. Sorig Bumshi embeds these numbers within a Bön cosmological and ritual context (e.g., 360 deities, mountains, and healing lakes), while Gyudshi reinterprets them under Buddhist causal reasoning (e.g., 404 diseases derived from wind, bile, phlegm, and karma). This transformation reflects a shift from Bön to Buddhist medical epistemology through selective integration and doctrinal refinement.