Andrographis paniculata is a source of diterpenoids and 2′-oxygenated flavonoids, which are of utility in pharmaceutical industry and ayurvedic formulations. With the aim of producing quality herb, an experiment was conducted with different combinations of bio-inoculants and vermicompost (VC) in controlled condition. It was observed that the highest Leaf:Stem (L:S) ratio, fresh herb yield and andro- grapholide yield (0.82, 300 g pot−1 and 29.8 g kg−1 dry herb, respectively) was recorded when the soil was incorporated with VC along with Azotobacter chrococcum (T3). Further there was a significant improve- ment in all soil fertility parameters. However, when all the bio-inoculants (A. chrococcum+Bacillus megaterium + Pseudomonas monteilii + Glomus intraradices) were mixed with VC, there was a significant improvement in soil dehydrogenase, alkaline, and acidic phosphatase activity. A positive correlation coefficient (p < 0.01) could be derived amongst plant growth, yield and soil properties (r = 0.45–0.85). The study suggests that application of the bio-inoculants and organic fertilizers can enhance productivity while maintaining the desired quality of the herb.