Canistel (Lucuma nervosa) is a valuable natural source of carotenoids, but their use in the food industry is hampered by low extraction efficiency, poor stability, and limited bio-accessibility. HPLC results showed that a deep eutectic solvent (DES) composed of D-menthol and canoic acid (Men-CaA) has significantly higher extraction yields for lycopene (498.66 ± 3.20 μg/mL DW) and β-carotene (6.43 ± 0.23 μg/mL DW) than corn oil. UV-VIS spectrophotometry combined with response surface methodology results confirmed that the best encapsulation efficiency of liposome for lycopene and β-carotene was attained in the temperature range of 30–70 °C, with the ratio of carotenoid extract to liposome of 1:25 (w/w), the ratio of phospholipids to cholesterol, and the ratio of aqueous phase to lipid phase of 2:1 (v/v). SEM analysis revealed that liposome-encapsulated carotenoid extract formed spherical structures with a uniform texture and rough surface. The ζ-potential assay confirmed the highest stability of liposomes at pH 7. FTIR spectroscopy indicated effective encapsulation of canistel-derived carotenoids by liposomes. Furthermore, liposomes encapsulation improved the thermal and storage stability and bio-accessibility of lycopene and β-carotene. Encapsulating canistel carotenoids in liposomes significantly enhances their stability and bio-accessibility, presenting a viable strategy for preserving the efficacy of food-based active ingredients.