Citrullus colocynthis (CC) has its own nutritional and therapeutical values. Peels of CC (CCPs) are usually discarded as a waste product and are not utilized. The current study underscores the CCPs to explore their pharmacological worth by focusing on their component's biological activities. The CCPs were collected from CC in Eldakhla, New Valley governorate, and the ethanolic method was used, followed by an evaporation process and dry freezing to obtain crude extract. Then, gas chromatography-mass spectrometry (GC-MS) was operated to detect various components in CCPs and WILEY 09, and the NIST14 mass spectral database was employed as a reference. GC-MS depicts the presence of different flavonoids, phenolics, nitrogen, and organophosphorus compounds in CCPs that have a huge value in medicine against acute and chronic illnesses. The results conclude superior components as phenol (1,1-dimethyethyl)-4-methoxy (12.52%), ursodeoxycholic acid (7.02%), 2-methoxy-4-vinylphenol (6.42%), 13-heptadecyn-1-ol (5.51%), hexadecanoic acid (5.49%), desulphosinigrin (4.29%), phenol, 4-(3-hydroxy-1-propenyl)-2-methoxy (3.99%), 16-octadecenoic acid, methyl ester (3.82%), 2,3-dihydro-benzofuran (3.65%), and trans-sinapyl alcohol (3.18%). These candidates have antioxidant, anti-inflammatory, anticancer, antidiabetic, antihypercholestermic, and antimicrobial bioactivities. Among the forty-five identified compounds in CCPs, the biological activities of only three weren't discovered. The results of this study would lead to pharmacological trials of the CCPs extract and its candidates on animal models.