Calotropis gigantea (L.) R. BR. (Asclepediaceae) is an evergreen, perennial shrub commonly known as “Sweta arka”. Plant exhibited medicinal and agricultural characteristics as they contain a rich source of bioactive metabolites. Ayurvedic and Indian medicinal systems (Charak and Sushruta Sanhita) have recommended the collection of the drug on time and place. The objective of the present work was to collect the plant on the lunar cycle and seasons to attain a good requisite therapeutic drug without additional exploitation of medicinal plant resources from the planet. All plant parts were collected from Maliba college campus on every Full moon and No moon days in winter, summer, and rainy season in the year 2016. An aqueous extract was obtained by sample-solvent ratio (0.5:10) of C. gigantea. Quantitative primary and secondary metabolite content were determined. Statistical analysis was expressed with principle component analysis that interprets all possible related variables. Results revealed that summer Full moon and No moon was a favorable season for total carbohydrate, tannin, total phenolic content and total flavanoid content respectively while total protein, and total cardiac glycoside content were pronounced in winter season No moon and Full moon respectively for Floral part. Rainy Full moon was favorable season for total protein, flavanoids, and total tannin content while rainy No moon was favorable for carbohydrate while winter Full moon and No moon was favorable for tannin and cardiac glycoside respectively for seeds. The observation of experimental studies validates the concept of seasons and lunar collection of C. gigantea for superior quality and maximum therapeutic yield of active principles.