BackgroundDue to the presence of several serious side effects such as erosion and bleeding in the gastric mucosal layer which are linked with Non-steroidal anti-inflammatory agents and a lot of these adverse effects may be dangerous for life and may cause numerous mortalities, demand for new antiinflammatory and analgesic agents has become an important task in medicinal chemistry to improve therapeutic efficacy as well as safety. MethodIn the search for new anti-inflammatory and analgesic molecules with greater potency, some novel indole derivatives (SK-1 to SK-9) were attained by chloroacetylation process of indole after that reaction through some aromatic aldehydes with the presence of acetic acid in absolute ethyl alcohol. IR, 1H NMR, and 13C NMR spectra were used for the structure elucidation of obtained chemical compounds. In this context, the analgesic and anti-inflammatory activity were evaluated for synthetically obtained new chemical compounds. Furthermore, the molecular docking studies were performed to elucidate the binding modes of synthesized ligands in the active pockets of Cox-1 / 2 enzymes. ResultAmong the compounds assessed, SK-2 and SK-8 demonstrated potent analgesic & anti-inflammatory activities when compared to ibuprofen and diclofenac sodium as reference drugs. Compound SK-4 has exhibited significant anti-inflammatory activity while compounds SK-1 and SK-5 have shown significant analgesic action when compared to the control. Molecular docking studies indicated that SK2 compound exhibited appreciable binding affinity (-9.16 kcal/mol) towards the COX-2 enzyme and mandatory interactions for COX-2 enzyme inhibition. ConclusionIt might be established from the present study that prepared compounds are unique in terms of their structure and noticeable biological action. In search of and initiation of a novel group of antiinflammatory and analgesic molecules, these compounds might be helpful.