Tuberculosis (TB) continues to be a significant worldwide infectious disease, causing substantial illness and fatalities. Prompt and precise diagnosis is essential for efficient treatment and management. Distinguishing between active tuberculosis (ATB) and latent tuberculosis (LTBI) is extremely difficult yet necessary for specific forms of treatment. The objective of this study is to discover and confirm diagnostic biomarkers that can differentiate between ATB and LTBI, thereby improving the accuracy of diagnosis and enhancing patient care. We employed high-throughput transcriptome and proteomic methods to examine samples from patients with active tuberculosis, latent tuberculosis infection, and healthy individuals. The techniques of RNA sequencing (RNA-Seq) and differential expression gene analysis were utilized to explore and characterize the patterns of gene expression. The investigation of differential expression was conducted utilizing Bioconductor packages in R (DESeq2). Our investigation has found a group of biomarkers that have unique expression profiles for active tuberculosis and latent tuberculosis infection. The expression levels of important genes such as IFNG, TNF, and IL6 were markedly increased in patients with active tuberculosis compared to those with latent tuberculosis infection and the control groups. This indicates the presence of an active inflammatory response that is characteristic of active tuberculosis disease. In contrast, biomarkers such as TCF7 and IL10 were discovered to be increased in patients with latent tuberculosis infection, indicating a connection with immune regulation and the continued presence of the virus in a dormant state. This study identifies potential biomarkers that can accurately distinguish between active and latent tuberculosis, thereby aiding in the development of more accurate diagnostic and treatment strategies for tuberculosis.