This study evaluated the toxicological effect of oral administration of Phoenix dactylifera seed essential oil (PDEO) in Wistar rats. PDEO was extracted through a steam-distillation technique. Acute toxicity study evaluated administration of a single dose of the oil in a group (n = 5) of rats followed by 24 h observation, for sub-acute toxicity evaluation, the animals were randomly divided into five groups (n = 3). Group 1 to 4 rats, respectively, received 62.5, 125, 250, and 500 mg/kg bw of PDEO for fourteen days, while the fifth group served as control. At the termination of the study, blood samples were obtained for biochemical and hematological analyses, while vital organs were histopathologically examined. Results from this study revealed no mortality or abnormal behavioral changes in the animals. A dose-related increase in bodyweight and hematological parameters was observed across the treated groups (p < 0.05). At a dosage of 500 mg/kg bw, PDEO caused slight elevation in biochemical marker levels and mild changes in histological architecture of liver and kidney of the test rats. This study revealed that PDEO exhibited significant hematopoietic attributes with no adverse effect on the experimental rats’ vital organs at concentrations below 500 mg/kg bw.