Medium-chain fatty acids (MCFA) are widely used in diets for patients with obesity. To develop a delivery system for suppressing dietary fat accumulation into adipose tissue, MCFA were encapsulated in nanoliposomes (NL), which can overcome the drawbacks of MCFA and keep their properties unchanged. In the present study, crude liposomes were first produced by the thin-layer dispersion method, and then dynamic high-pressure microfluidisation (DHPM) and DHPM combined with freeze–thawing methods were used to prepare MCFA NL (NL-1 and NL-2, respectively). NL-1 exhibited smaller average size (77·6 (sd 4·3) nm), higher zeta potential ( − 40·8 (sd 1·7) mV) and entrapment efficiency (73·3 (sd 16·1) %) and better stability, while NL-2 showed narrower distribution (polydispersion index 0·193 (sd 0·016)). The body fat reduction property of NL-1 and NL-2 were evaluated by short-term (2 weeks) and long-term (6 weeks) experiments of mice. In contrast to the MCFA group, the NL groups had overcome the poor palatability of MCFA because the normal diet of mice was maintained. The body fat and total cholesterol (TCH) of NL-1 (1·54 (sd 0·30) g, P = 0·039 and 2·33 (sd 0·44) mmol/l, P = 0·021, respectively) and NL-2 (1·58 (sd 0·69) g, P = 0·041 and 2·29 (sd 0·38) mmol/l, P = 0·015, respectively) significantly decreased when compared with the control group (2·11 (sd 0·82) g and 2·99 (sd 0·48) mmol/l, respectively). The TAG concentration of the NL-1 group (0·55 (sd 0·14) mmol/l) was remarkably lower (P = 0·045) than the control group (0·94 (sd 0·37) mmol/l). No significant difference in weight and fat gain, TCH and TAG was detected between the MCFA NL and MCFA groups. Therefore, MCFA NL could be potential nutritional candidates for obesity to suppress body fat accumulation.