Abstract: Solanum muricatum, a unique cash crop in Yunnan Province, faces several significant challenges in its primary cultivation areas due to prolonged use of chemical fertilizers and pesticides. These challenges include soil acidification, compaction, low organic matter, declining fertility, severe crop diseases, and reduced yields. This study aimed to explore the impact of bio-organic fertilizer (BOF) on soil quality, enzyme activity, leaf blight incidence, and Solanum muricatum yields in a region with acidic and degraded soil conditions at a high plateau. Four different application rates of BOF (9, 12, 15, and 18 t/hm²) were tested, with a control group using 150 kg/hm² of urea (CK). The findings indicated significant improvements (P<0.05) in various soil parameters, such as pH, electrical conductivity (EC), cation exchange capacity (CEC), organic matter content, and available nutrients, as well as increased activity of soil enzymes like phosphatase, urease, and polyphenol oxidase. Furthermore, a noticeable decrease (P<0.05) in soil bulk density was observed. Compared to the CK group, the application of BOF led to an enhanced Solanum muricatum yield by improving soil physicochemical properties and increasing soil enzyme activity, with an interpretation rate of 87.40%. Additionally, BOF application significantly reduced leaf blight in Solanum muricatum (P<0.05), and a significant logarithmic relationship was observed between Solanum muricatum yield (R² = 0.794, P<0.01). Notably, in the presence of obstacles, the use of BOF at rates of 15–18 t/hm² led to higher Solanum muricatum yields compared to non-obstacle planting areas. In conclusion, substituting chemical fertilizers with biomass organic fertilizer can substantially enhance soil physicochemical properties, reduce plant disease incidence, and increase Solanum muricatum yields.