Nasopharyngeal cancer is a malignancy developing from the nasopharynx epithelium due to smoking and nitrosamine‐containing foods. Nasopharyngeal cancer is highly endemic to Southeast Asia. Eugenol and piperine have shown many anticancer activities on numerous cancer types, like colon, lung, liver, and breast cancer. In this study, we amalgamated eugenol and piperine loaded with a polyhydroxy butyrate/polyethylene glycol nanocomposite (Eu‐Pi/PHB‐PEG‐NC) for better anticancer results against nasopharyngeal cancer (C666‐1) cells. In the current study, nasopharyngeal cancer cell lines C666‐1 were utilized to appraise the cytotoxic potential of Eug‐Pip‐PEG‐NC on cell propagation, programmed cell death, and relocation. Eu‐Pi/PHB‐PEG‐NC inhibits cellular proliferation on C666‐1 cells in a dose‐dependent manner, and when compared with 20 µg/ml, 15 µg/ml of loaded mixture evidently restrained the passage aptitude of C666‐1 cells, this was attended with a downregulated expression of mitochondrial membrane potential. Treatment with 15 µg/ml Eu‐Pi/PHB‐PEG‐NC suggestively amplified cell apoptosis in the C666‐1 cells. Furthermore, its cleaved caspase‐3, 8, and 9 and Bax gene expression was augmented and Bcl‐2 gene expression was diminished after Eu‐Pi/PHB‐PEG‐NC treatment. Additionally, our data established that the collective effect of Eu‐Pi/PHB‐PEG‐NC loaded micelles inhibited the expansion of C666‐1 cells augmented apoptosis connected with the intrusion of PI3K/Akt/mTOR signaling pathway.