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Objectives: Cuminaldehyde self‐emulsified nanoemulsion (CuA‐SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. Methods: Cuminaldehyde self‐emulsified nanoemulsion was developed through the self‐nanoemulsification method using Box–Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA‐SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in‐vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. Key findings: Cuminaldehyde self‐emulsified nanoemulsion with acceptable characteristics (mean DS‐48.83 ± 1.06 nm; PDI‐0.232 ± 0.140; ZP‐29.92 ± 1.66 mV; EE‐91.51 ± 0.44%; and drug‐loading capacity (DL)‐9.77 ± 0.75%) was formulated. In‐vitro drug release of CuA‐SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA‐SEN to CCl4‐induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA‐SEN reduced the levels of tumour necrosis factor‐alpha and interleukin‐6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. Conclusions: These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti‐inflammation and antihepatotoxicity of the drug. [ABSTRACT FROM AUTHOR]