Objective: The Gandhamardan Hills (GMH)range is a group of small mountains in Peninsular India in Balangir district in Odisha state in India. There is uniqueness in geology, geography, geomorphology, climatology, Hydrology, petrology, and lithology. The lithology, soil, water, geomorphology, and traditional use of plants in Ayurveda (India) have holistic medicinal/surgery. origin. Geo-hydro-biological amalgamation through Geological Information Systems (GIS) and chemical analysis is still being explored, and the present research emphasises such studies. Methods: Data about geo-hydro-biology through grapy, geology, geomorphology, hydrology, and traditional medicinal practices are implored from literature sources, using TOPO and Q-GIS maps and ERDAS software; their analytical interpretations were reported. The chemical analysis was conducted using X-ray fluorescence spectrometric studies of the water and soil of GMH, and the exuberance of ethnobotanical species in GMH was correlated. Results Laboratory analysis, literature studies, and interaction with Ayurvedic and Kaviraj practitioners, 154 popular species databases with their pharmacological applications reported for ordinary people. Many species have multidimensional applications that can transform Ayurveda into Materia medica. Conclusion: This ethnobotanical study documented the use of plants by the local community. The natural medicinal plants are cheap for the rural communities. The information gathered can be used for further scientific investigation to develop new commercial plant-based medicines as they will be safer than synthetic drugs. SDGs 1 to 3 and 12, 13, and 15 will be satisfied if we can conserve and adequately manage the hub of medicinal plants in GMH.