Background: Diabetic nephropathy (DN) is one of the most well-known diabetic microvascular complications, affecting around 40% of individuals with type 2 diabetes mellitus (T2DM). It progresses to end-stage renal disease (ESRD), and its primary detection can be done via diabetes biomarkers. The power of early biomarker identification of DN in T2DM serum is evaluated in this study. Aim: This study aimed to assess the possibility of using ΒTP and Cys. C as earlier markers for the detection of nephropathy in patients with type 2 DM. Materials and Methods: This is a cross-sectional study. It included one hundred twenty patients with T2DM, composed of 66 males and 45 females, and aged 40–69 years, who were divided into 3 groups by using the urinary albumin/creatinine ratio (ACR): Group I: (N = 40 Normoalbuminuria UACR < 30 mg/g as control), Group II: (N = 40 Microalbuminuria UACR 30–300 mg/g), Group III: (N = 40 Macroalbuminuria UACR ˃ 300 mg/g). In all groups, βTP and Cys. C were estimated in the serum of patients, and both biomarkers had the same methodology by quantitative enzyme immunoassay (double-antibody sandwich).