This study presents the efficient synthesis of a novel series of pyrazole-thiosemicarbazone derivatives (3-7) from a key precursor (2) via cyclization with α-halocarbonyl compounds. The structures of all synthesized hybrids were unequivocally confirmed through elemental analysis and comprehensive spectral studies (IR, NMR, MS). Among them, in vivo anti-inflammatory evaluation in a carrageenan-induced paw edema model identified compounds 3 and 4 as exceptionally potent, exhibiting significant inhibition rates of 66.67% and 73.08%, respectively. Molecular docking studies revealed strong and favorable binding interactions of these lead compounds with the active sites of cyclooxygenase enzymes (COX-1 and COX-2), providing a rational structural basis for their observed efficacy. Furthermore, in silico pharmacokinetic predictions indicated that 3 and 4 possess promising drug-likeness and oral bioavailability …