One of the most coveted objectives for healthcare research in recent years has been the ability to evaluate physiological states, track illness development and progression, and track post-treatment therapeutic outcomes using a non-invasive method. In this sense, saliva analysis can be viewed as a very intriguing biological matrix for general health and disease surveillance. Salivary levels of potentially significant indicators rise during both local and systemic inflammation. In this study, a very sensitive biosensor for TNF- \(\alpha \) detection in human saliva was created. In order to increase detection sensitivity, decrease analysis times, and concurrently detect various cytokine indicators, fully integrated electrochemical immuno-sensors platform was developed. Then, TNF- \(\alpha \) was identified using a sandwich-type detection method in a TMB solution employing the labeled antibody Ab-TNF-HRP activity. By analyzing solutions containing potential salivary interferences, such as interleukin-10 (IL-10) and the hormone cortisol, which are both released during the acute stage of inflammation, the immune-specificity sensor’s was examined in the ideal experimental conditions. With a limit of detection (LOD) of 1 pg ml \(^{-1}\) , the developed immuno-sensors shown good performance for Ag-TNF-cytokine chrono-amperometric detection in the range of 1 pg ml \(^{-1}\) to 30 pg ml \(^{-1}\) . In second step, using eight gold-working microelectrodes (WE). Through functionalization with carboxyl diazonium, the monoclonal antibodies (mAb) anti-human tumor necrosis factor-alpha (anti-TNF- \(\alpha \) ) were bound onto gold WE. TNF- \(\alpha \) cytokines were examined in PBS buffer, synthetic saliva, and actual human saliva in the \(1-100\) pg ml \(^{-1}\) range, which is the important range for heart failure patients. The initial preliminary findings from EIS studies of human saliva produced a result 3.1 pg ml \(^{-1}\) , which is quite encouraging for quick cytokine detection analysis.