Corydceps guagndongensis, a novel edible-medicinal fungus in China, was found and successfully domesticated by our team. Its fruiting body has plenty of nutritional and bio-active ingredients, and shows many obviously medicinal functions such as improving chronic renal failure and chronic bronchitis. Therefore, we carried out the analyses of omics, gene function and bio-active functions of C. guangdongensis. According to WGCNA analysis during the process of growth and development, we identified 1135 hub genes, and found that genes related to heat shock proteins and transcriptional factors as well as bio-active compounds biosynthesis were differentially expressed. Meanwhile, sRNA sequencing identified 26 conserved milRNAs and 19 novel milRNAs, and 20 milRNAs were significantly differentially expressed during the process of growth and development. Based on the genome information of C. guangdongensis, 22 genes encoding DnaJ protein were identified, and the silence of DnaJ05 obviously inhibited mycelial growth and primordial formation of C. guangdongensis. Melatonin and the intermediates were quantitatively detected under different experiment conditions, further analyzing the biosynthesis pathway and the potential function of melatonin in C. guangdongensis. In addition,animal tests showed that C. guangdongensis lipid-lowering formula and ethanolic extract significantly decreased body weight, improving glucose tolerance and non-alcohol fatty acid liver disease, reducing white fat weights and blood lipid indexes, increased the relative abundances of beneficial gut microbiota (Bacteroides and Bifidobacterium), and promoted short chain fatty acid production. These results provide theoretical basis for variety breeding and the application of C. guangdongensis in food and bio-medicine as well as health-care industries.