Recently, nanoparticles (NPs) of different compositions and dimensions have become used as versatile and sensitive tracers [1]. The creation of designer NPs for enhanced sensitivity in sensing applications greatly benefits from their small size, where their properties are strongly influenced by increasing their surface area [2–7]. Indeed designer NPs are one of the most exciting areas in modern electroanalytical analysis because they offer excellent prospects for creating highly sensitive and selective assays. Electrochemical sensing methods based on the modification of particular metal NPs on conductive substrates is a fascinating and quickly expanding research area [8–12]. The remarkable electrochemical features of metal NP-modified electrodes are now widely employed in conventional systems. To reduce the use of reagents and the required electroanalysis time, a miniaturized system has been introduced. In this manuscript, the metal-NP electrochemical sensors used for electroanalytical purposes, especially, in bioapplications are reviewed. Biochemical substances are one of the essential companions of life on earth, it has been central to the evolution of human civilizations in healthy. Therefore, even since the discovery of metal-NP, researchers have been exploring their potential in bioapplications, which made these applications are the most expanded in recent years. One of the reasons to focus on the use of metal-NP based electrochemical detection in bioanalysis may be concern the importance of the diagnosis and prevention of diseases. Indeed, metal-NPs have many interesting and unique properties potentially useful in a variety of biological and biomedical systems and devices. Such the mentioned inspirations, the electrochemical characteristics of metal NPs and the sensing applications derived from these materials are discussed, and their advantages and weaknesses are explored. We envisage a promising future for the use of these metal-NP-modified electrodes in both conventional and miniaturized systems.