Keloids are benign tumors that result from abnormal wound healing. These growths may cause cosmetic and functional problems, especially when they grow in the joint area. Although the pathogenesis is not fully understood, stimulated fibroblasts cause excess collagen deposition in the extracellular matrix, leading to keloid formation. They also synthesize cytoglobin, the overexpression of which can protect against the fibrotic process. At present, keloid therapy remains unoptimized, primarily because keloids often experience recurrence after treatment. Therefore, studies to find keloid therapy are still being carried out. This study explored the effect of ethanol extract of Uncaria gambir (EG) on the expression of cytoglobin, elastin, desmosine, and collagen type I, and III of keloid fibroblasts. Fibroblasts were isolated from keloid and non-keloid skin tissues using primary culture techniques. An enzyme-linked immunosorbent assay (ELISA) method was used to determine the expression of cytoglobin, elastin, and desmosine. Meanwhile, immunocytochemistry was used to determine collagen I and III expression. The results showed that EG increased the expressions of cytoglobin, elastin, and desmosine while reducing the expression of collagen types I and III. EG is likely to have potential as an anti-keloid. © 2025 Society of Pharmaceutical Sciences of Ankara (FABAD). All rights reserved.