Novel N-substituted Indole derivatives with various hetero-cyclic moieties were synthesized via an ethyl linker in order to obtain highly potent anti-inflammatory and antioxidant agents. The structure of the obtained chemical compounds was determined using IR, 1 H-NMR, and mass spectroscopy. Molecular docking was used to create selective and efficient COX-2 inhibitors from twelve novel indole derivatives (11a-c, 12a-c, 13a-c, and 14a-c). The compounds 13b and 14b had a high interaction energy, which inhibited the COX-2 enzyme. There is a relationship between anti-inflammatory activity and antioxidants, which is also defined by COX-2 inhibition, according to the mechanism of action. The Swiss ADME online programme was used to determine the drug-like properties of synthesized compounds. Two common and reliable methods were adopted to determine the antioxidant effect. In the DPPH assay, compounds 11a, 11b, and 14b, whereas compounds 11b, 13b, and 14b in the reducing power assay, were the most potent as compared with standard ascorbic acid. To evaluate the anti-inflammatory effect at an acute and chronic level, the carrageenan-induced paw edema method along with the formalin-induced inflammation method were used both at low dose and high dose. From the collected results, compounds 13b and 14b were the most potent against acute and chronic inflammation. The results showed that the synthesized compounds are unique as anti-inflammatory and antioxidant agents, and that they could be useful for drug discovery in the future.