Betulinic acid, a plant secondary metabolite, has gained significant attention due to its antiproliferative activity over a range of cancer cells. A promising betulinic acid analogue (2c) with better therapeutic efficacy than parent molecule to colon carcinoma cells has been reported. Despite impressive biological applications, low aqueous solubility and bioavailability create difficulties for its therapeutic applications. To overcome these lacunae and make it as a promising drug candidate we have encapsulated the lead betulinic acid derivative (2c) in a polymeric nanocarrier system (2c-NP) and evaluated its in vitro and in vivo therapeutic efficacy. Apoptosis that induces in vitro antiproliferative activity was significantly increased by 2c-NP compared to free-drug (2c), as assured by MTT assay, Annexin V positivity, JC1 analysis and cell cycle study. The therapeutic potential measured in vitro and in vivo reflects ability of 2c-NP as an effective therapeutic agent for treatment of colon carcinoma and future translation to clinical trials.