The cephalopod digestive gland (DG) is responsible for enzyme production as well as nutrient and lipid storage. Octopus maya (Mollusca: Cephalopoda) is a holobenthic octopus species with aquaculture potential. To develop a balanced food for the rearing of this octopus, it is necessary to understand its digestive physiology. We performed histological studies on the structural change of the DG (cytological ontogeny) associated with age (from 0 to 30 d posthatching, DPH) and food (postprandial change in 120 DPH juveniles). Early ontogeny of DG was defined in 3 stages: (1) yolk platelets stage (0 to 5 DPH), (2) transition stage (6 to 10 DPH) and (3) heterolysosomes (food reserves) stage (>12 DPH). In Stage 1, the DG had anatomically undifferentiated tubules, but was filled with yolk platelets. The tubular structures developed lumen by 5 DPH. Stage 2 (starting at 6 DPH) corresponds to mixed exogenous and endogenous feeding. At that time, the yolk platelets were gradually consumed until completely exhausted at 9 DPH. At the onset of Stage 3, the DG structure was completely tubular, exhibiting digestive cell microvilli and other cellular features typical to octupus DGs. During exogenous feeding (12 DPH and onward), acidophilic secretory lysosomes, heterolysosomes and some heterophagosomes appeared on DG cells. O. maya has long digestive cycles in which the extracellular and intracellular digestion can take up to 8 h. Although the ecological implications of this information for aquaculture will still have to be proven, results demonstrated that O. maya is an energetically efficient species and thus suitable for rearing in captivity.