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Testicular toxicity is recognized as an underlying factor contributing to male infertility. This study evaluated the protective effects of Artemisia herba-alba against calcium tetrachloride (CCl₄)-induced toxicity in rats, focusing on its impact on ERCC1 gene expression. 20 male Wistar rats were randomly divided into four groups (n = 5 per group). Group I served as the untreated control. Group II received oral CCl₄ (0.4 ml/200g) every other day for three weeks. Group III was administered Artemisia herba-alba (ART) extract orally at 500 mg/kg body weight every other day for three weeks. Group IV was treated with both ART extract (500 mg/kg b.w.) and CCl₄ (0.4 ml/200g) on alternating days over three weeks. Parameters assessed included body weight, relative kidney weight, serum testosterone, tissue oxidative stress markers, ERCC1 gene expression, and testicular histology. The results revealed that CCl₄ exposure led to reduced body weight, lower tissue glutathione (GSH), decreased serum testosterone, elevated lipid peroxidation, upregulated ERCC1 expression, and disrupted testicular histoarchitecture. Conversely, ART co-treatment mitigated these effects, improving testicular histology, downregulating ERCC1 expression, and partially preserving body weight and testosterone levels. Further research with extended treatment periods is recommended to confirm the therapeutic potential of ART in managing testicular toxicity.