Dietary bioactive molecules offer great potential in the fight against life style disorders such as obesity, diabetes, cancer and cardiovascular disease through modulating the key cellular signaling pathways as well as their strong antioxidant potential. Obesity has emerged as one of the biggest public-health concern as it is the major risk factor for developing type II diabetes, cardiovascular disease, hypertension and certain types of cancer. Fucoxanthin, a dietary carotenoid from marine brown algae contains unique functional groups such as epoxide and allenic bond, has been reported to show anti-obese potential. Curcumin is a widely studied biphenolic compound from Indian traditional spice, turmeric for its beneficial health effects. Recent studies emphasize that the protective effects of some single dietary molecules are potentiated and/or synergized by other dietary agents. In the present study, we investigated the anti-obese potential of fucoxanthin in combination with curcumin in a KK-Ay mice model system. Administration of fucoxanthin, curcumin and their combination reduced the body weight compared to control group. These molecules when administrated alone or in combination did not affect the blood levels of two major liver function markers such as aspartate transaminase (AST) and alanine amino transferase (ALT). Further, the weight of kidney and liver did not change by the administration of fucoxanthin, curcumin and their combination. But, total white adipose tissue (WAT), epi-didymal WAT and mesenteric WAT were significantly reduced in combination group. An increase in HDL cholesterol and phospholipid content also observed in combination group. Our findings demonstrate the promising anti-obese efficacy of combinatorial effect of fucoxanthin and curcumin. Further, our results provide experimental support to the hypothesis that dietary molecules in combination might elicit greater protection against obesity, which deserves further mechanistic investigations.