System biology could unveil the unknown effects of the plant. Although the herbal medicine have been used for a long time as a traditional herb, the finding way of the active compounds and effects remain unclear. This study integrated a network-based analysis and biochemical experiments to confirm the herb’s therapeutic effects on the oxidative injury. Our study identified the active components and the biochemical mechanisms based on the multiscale interactome (MSI). Some beneficial herbs inhibited the oxidative damage by acting on the several beneficial pathways and cell-protective signaling transductions such as AMPK and Hippo/YAP as assessed by MSI and the cell-based analysis. This study provide a strategy to elucidate to find the new indication as well as active components in the herbal medicines. This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (number: HF20C0212), and the National Research Foundation of Korea (NRF) grant funded by the Korea Government [MSIP] (RS-2023-00218419).