| Introduction: The survival of Cultural Ecosystem Services, specifically Indigenous Knowledge (IK) of medicinal plants in Southern Iran, is undergoing rapid erosion due to accelerated generational shift and modernization. This study moves beyond simple documentation in the Hormozgan biodiversity hotspots (Minab and Rudan Counties), aiming to quantify, validate, and identify candidate species for novel phytochemical exploration. Methodology: A comprehensive cross-sectional study was conducted, where deep, semi-structured interviews were performed with 31 Key local informants, focusing on the inter-generational transfer of knowledge. Data on the number of species, preparation methods, and therapeutic uses were analyzed using established quantitative ethnobotanical indices, namely the use reports (UR) relative frequency index (RFC), Cultural index (CI), and the Informant Consensus Factor (ICF), to optimize the pharmacological screening process. Key Findings: A total of 118 medicinal plant species across 44 plant families were registered. Our analyses showed that treatments for Dermatological, gastrointestinal, and respiratory disorders commanded the highest consensus among informants (ICF > 0.90). The ethnobotanical survey demonstrated that the Lamiaceae, Asteraceae, and Fabaceae were the most represented and highly utilized plant families, with 1,347 use reports documented across all taxa. The primary plant parts employed, in descending order of frequency, were leaves, flowers, fruits, and roots. The predominant preparation methods were decoction, followed by poultice and infusion. These reports were categorized into 14 use categories addressing 79 distinct diseases. The most dominant medicinally utilized plant species were identified as Cynanchum acutum, Cymbopogon iwarancusa, Matricaria aurea, Malva neglecta, and Lawsonia inermis, respectively. Furthermore, 41% of the recorded therapeutic applications were identified as novel indigenous uses not previously documented in any major national or international medicinal plant databases, suggesting a unique biochemical reservoir in the region. Conclusion and Implications: The findings provide an immediate roadmap for the targeted screening of active compounds from the Minab and Rudan flora. Prioritizing species with the highest cultural weight (high CI) significantly increases the probability of discovering new bioactive molecules. The urgent conservation of this unique IK and its associated botanical reserves is a critical conservation priority that will secure the region's pharmaceutical potential and bio-economy. |