Obesity is a major public health problem worldwide and a risk factor for certain diseases, including cardiovascular disease, diabetes, cancer, and depression. Unfortunately, currently available anti-obesity drugs have failed in the long-term maintenance of weight control. It has been a challenge to design novel drugs that could potentially treat obesity or prevent uncontrolled weight-gain which lies underneath the pathology of obesity. Since obesity in a way is a consequence of the accumulating new mature adipocytes from undifferentiated precursors which is a process also termed as adipogenesis, drugs that might control adipogenesis could be beneficial for the treatment of obesity. In the current study, combined effect of sodium pentaborate pentahydrate (NaB) and pluronic F68 on adipogenic differentiation was examined by administering various combinations of the two agents to human adipose-derived stem cells (hADSCs) in in vitro. Immunocytochemistry and quantitative RT-PCR were performed to evaluate the levels of adipogenesis-promoting genes such as peroxisome proliferator-activated receptor-gamma (PPAR gamma), fatty acid binding protein (FABP4), and adiponectin. Results indicated that expressions of all these three genes were restrained. Furthermore, Oil Red O staining revealed that lipid vesicle formation was reduced in hADSCs treated with differentiation medium containing NaB/F68 combination. Finally, expression levels of Hippo pathway kinases Lats2, MST1, and scaffold protein Sav1 were reduced in these cells, suggesting a possible link between Hippo pathway-dependent downregulation of PPAR gamma and the NaB/F68 treatment. Herein, we showed that combination of NaB and F68 curtails adipocyte differentiation by inhibiting the adipogenic transcriptional program leading to a decrease in lipid accumulation in adipocytes even at very low doses, thereby uncovered a striking opportunity to use this combination in obesity treatment.