Cuscutae Semen mainly includes salt-processed product (SPP) and wine-processed product (WPP), which are most commonly used in traditional Chinese medicine. However, the differences between SPP and WPP have not been reported. In this paper, comparative studies between SPP and WPP on chemical contents and effect in kidney-yang deficiency rats have been investigated. UPLC-MS/MS was used to study the differences in chemical components. Kidney-yang deficiency was induced by hydrocortisone in rats. Rats were orally administrated with different doses of Jinkui Shenqi Pills, SPP, and WPP for 28 days. The average organ coefficients, renal function indexes, sex hormone levels, and testicular morphology were detected. As a result, the contents of flavonoids and chlorogenic acids were higher in SPP than in WPP, which may be caused by different processing methods. The improvement on reproduction of SPP was reflected in organ coefficients, renal function indexes, and biochemical properties of seminal plasma; furthermore, WPP was in sex hormone levels and morphology of testis. As a conclusion, these results indicated that both SPP and WPP can improve the reproductive function of kidney-yang deficiency rats with different mechanisms, which may be due to the differences in chemical contents between WPP and SPP as well as different processing methods. It is the first time that the differences between SPP and WPP have been studied in reproductive function in rats with kidney-yang deficiency.