Berberine has been used for the treatment of diseases such as diabetes, gastroenteritis, polycystic ovary syndrome, etc.[29] Previous studies have shown that berberine can inhibit the deubiquitination activity of CSN5, reduce the expression of PD‐L1 in cancer cells, and promote antitumor immunity.[30] In this study, we found that B68, a derivative modified from berberine, targets CSN5 with an effect similar to that of berberine and can reduce the level of PD‐L1. This evidence concerns the gene CD274 and diabetes mellitus.