A non-enzymatic reaction between reducing sugars (glucose) and lysine and arginine, formally known as glycation, has potentially adverse effects in protein structure and function. Glycation can progress to the formation of fluorescent and non-fluorescent advanced glycation end product (AGEs) such carboxymethyllysine (CML), carboxyethyllysine (CEL), and covalent protein crosslinking adducts. Glycation and formation of AGEs have been implicated in the development of complications in diabetes. The Cucurbitacae family has been known for its hypoglycemic activity in folk medicine but the individual compound(s) responsible for preventing diabetic complications through inhibition of AGE formation remains undocumented. Aminoguanidine (AG), a proven in vitro AGEs inhibitor, showed side effects in clinical trials. AG was used as model of glycation the non-enzymatic reaction of histone H1 and ADP-ribose. Cucurbita andreana extract was fractionated using various chromatographic tools followed by detection of AGE inhibition through fluorescence spectrophotometry, sodium duodecyl sulfate poly-acrylamide gel electrophoresis (SDS-PAGE), ion-exchange chromatography and RP-HPLC. Total Cucurbita andreana extract showed up to 94% fluorescence, crosslinks, CML, and CEL protein adduct inhibition at equivalent or higher percentages than AG. Fractions containing primarily cucurbitacin E-glycoside and cucurbitacin D have shown dose-dependent fluorescence inhibition approximately 17% higher than AG at comparable molar concentrations. These results suggest that cucurbitacins might potentially be recommended as a supplement in prevention of diabetes complications.