Cannabidiol (CBD) has significant therapeutic potential; nevertheless, its advance as an effective drug by the pharmaceutical business is hindered by its inherent characteristics, such as low bioavailability, low water solubility, and variable pharmacokinetic profiles. This research aimed to develop nanoliposomes using an easy and low-cost method to improve the hydrosolubility of CBD and achieve a controlled delivery of the active principle under relevant physiological conditions from the mouth to the intestine; the cytotoxic and antitumor activities were also evaluated. To achieve the objective, core-shell nanoliposomes based on CBD were synthesized in three easy steps and characterized in terms of shape, size, surface chemistry, thermal capacity, and surface charge density through transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and potential charge (PZ), respectively. CBD-controlled delivery trials were carried out under simulated mouth-duodenal conditions and fitted to Korsmeyer-Peppas and Noyes-Whitney models to conclude about the pharmacokinetics of CBD from nano-CBD. Cytotoxicity studies on nonmalignant human keratinocytes (HaCaT) were carried out to evaluate its safety and the recommended consumption dose, and finally, the antiproliferative capacity of nano-CBD on human colon carcinoma cells (SW480) was determined as beginning proposal for cancer treatment. The characterization results verified the water solubility for the CBD nanoencapsulated, the core-shell structure, the size in the nanometric regime, and the presence of the synthesis components. The dissolution rate at duodenal conditions was higher than that in buccal and stomach environments, respectively, and this behavior was associated with the shell (lecithin) chemical structure, which destabilizes at pH above 7.2, allowing the release by non-Fickian diffusion of CBD as corroborated by the Korsmeyer-Peppas model. In vitro biological tests revealed the innocuousness and cyto-security of nano-CBD up to 1000 mg·L-1 when evaluated on HaCaT cells and concentrations higher than 1000 mg·L-1 showed antitumor activity against human colon carcinoma cells (SW480) taking the first step as a chemotherapeutic proposal. These results are unprecedented and propose a selective delivery system based on nano-CBD at low cost and that provides a new form of administration and chemo treatment.