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Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi\u2010timepoint drug administration strategies across a wide range of drugs. Here, droplet\u2010engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici\u2010plate as an in vitro high\u2010throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (<jats:italic>Cry1<\/jats:italic>) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time\u2010dependent variations are demonstrated in toxicity on the Chronotoxici\u2010plate, highlighting the importance of considering time\u2010dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. 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