The nanoencapsulation of essential oils enhances their applicability in several areas, such as pharmaceuticals and food biopreservation. This study focuses on the encapsulation of Saccocalyx satureioides Coss. et Durieu essential oil into nanoemulsions by high-pressure homogenization (HPH) and its effect on the volatile constituents and the antioxidant and anticancer activities of the essential oil. The analysis of hydrodistilled (HD) S. satureioides essential oil using gas chromatography–mass spectrometry revealed a total of 28 constituents, representing 99.80%, while only 13 constituents were identified in nanoemulsions, representing 98.65% of the total volatile material. The use of HPH led to qualitative and quantitative differences between the volatile profiles of the HD and the nanoemulsion of S. satureioides essential oil. Whereas borneol, α-terpineol, and thymol were the predominant constituents in the HD oil, carvacrol, thymol, and γ-terpinene were the major constituents in the nanoemulsion. The antioxidant activity of the S. satureioides essential oil nanoemulsion displayed was lower as compared to that of HD oil using DPPH free radical–scavenging, CUPRAC, and ABTS assays. This is consistent with the differences in total flavonoid, total phenolic, and volatiles detected in both HD oil and its nanoemulsion. Meanwhile, the cytotoxicity on liver cancer cells (Hep-G2) was stronger using nanoemulsions (106 μg/mL) than using HD oil (274.8 μg/mL).