Paramount efforts by pharmaceutical industry to identify new targets for obesity-diabetes (Diabesity) pharmacological intervention have led to a number of agents developed and directed at DPP IV [dipeptidyl peptidase IV] enzyme inhibition thereby enhancing endogenous insulinotropic incretins. Besides antioxidative-antiinflammtory molecules that inhibit accumulation of advanced glycation end products (AGEs) can be good candidates for ameliorating diabetic complications. Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). The suggested association between obesity and colorectal cancer initiated the evaluation of antiproliferative activity of the new FQs and TFQs against a panel of obesity related colorectal cells (HT29, HCT116, SW620 CACO2 and SW480). The aim of the current study is to examine the potential of newly synthesized FQs and triazolofluoroquinolones (TFQs) derivatives as dual inhibitors for glycation and inflammation, DPP IV inhibitors, PL inhibitors for dual management of obesity and diabetes, as well as antiprolifertaive efficacy against colorectal cancer cell lines. Sulforodamine B (SRB) colorimetric assay revealed that some derivatives exhibited unselective cytotoxity against HT29, HCT116, SW620 CACO2 and SW480. The superior antiglycation activity of the reduced derivatives 4a and 4b over that of aminoguanidine with respective IC50 (μM) values of 3.05±0.33 and 8.51±3.21; none of the tested synthetic compounds could perform equally effectively to Diprotin A, a dose dependent inhibitor of DPP IV. Compounds 4a, 5a, 3b, 4b and 5b demonstrated anti-inflammatory IC50 values exceeding that of indomethacin. Compounds 3a and 4a showed IC50 lower than 10 μM as PL inhibitors. In conclusion, FQ and TFQ derivatives may unveil new antiobesity and anticancer agents in the future. Our research qualifies FQs and TFQs as promising candidates for the development of related α-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress.