development of the soil structure 2) . They enhance the soil structure by improving macro-porosity, which exerting their impact on water dynamics, aeration, and decomposition of inorganic and organic materials 3,4) .Various components of earthworms have been employed as therapeutic drugs against different infectious illnesses since 1340 AD 5) . The defensive system of earthworm lacks antibodies in their blood circulatory system but their body extracts and coelomic fluid comprise of different bioactive agents (i.e. peptides and proteins) that defend these worms 6) . Literature has revealed that earthworm s body extracts (i.e. coelomic fluid) contain different biologically active peptides and proteins that has potential effect as cy-Abstract: Humoral practice is a fundamental natural biological phenomenon in earthworm defensive system which protects them from infectious bacteria and irritating agents by different mechanisms. The defensive system of earthworms is highly complicated because they lack antibodies in their blood circulatory system but their body extracts and coelomic fluid comprise of different bioactive agents (i.e. peptides and proteins) that defend these worms. There are various groups of bioactive agents such as proteases (name depends on proteins/peptide function or formal earthworm species name), metabolites (total 59 metabolites found in Eisenia fetida), metal binding proteins (2 proteins such as Ca 2+ binding calmodulin and metallothionein), active proteins (include lysozyme, lysenin and eiseniapore etc.), antimicrobial peptides (antibacterial vermi-peptides family (AVPF), antimicrobial peptide I (PP-I), coelomic cytolytic factor (CCF, CCF-I and CCF like protein), fetidin, lysenin, lumbricin (lumbricin I, lumbricin PG, and lumbricusin), organic acids (fatty acids, succinic acids, and lauric acid) and other organic compounds (such as purine and vitamin D). The presence of above mentioned molecules confer therapeutic potential that affect energy intake and involve in decreasing oxidative stress, metabolic disturbances and pro-inflammatory conditions. The future perspectives of earthworm bioactive compounds are concerned with the development of provisional standards, purification and classification for utilizations in pharma industry.