Fullerene Black (FB) and Extracted Fullerene Black (EFB) were used in modified screen‐printed electrodes producing electrochemical transducers (FB‐SPEs and EFB‐SPEs). A complete electrochemical study was performed and the best results are obtained working with FB‐SPEs, especially in terms of: 1. improved electron‐transfer kinetic mechanisms and 2. sensitivity and selectivity toward Acetaminophen (Ac) and Guanine (G). These latter represent two important electro‐active targets to quantify in medicine field application, because: Ac is a preferred alternative (as analgesic‐antipyretic agent) to aspirin, particularly for patients who cannot tolerate aspirin; the oxidation signal of G is useful for the fabrication of emerging analytical tools, such as DNA chipsand user‐friendly diagnostic devices. Ac and G are quantify by using FB‐SPEs electrochemical devices, with an extended linearity (1–300 μM for Ac; 0.1–300 μM for G), an excellent sensitivity (2.82 μA μM−1 cm−2 in the case of Ac; and 0.183 μA μM−1 cm−2 in the case of G), a low detection limit (0.01 μM for Ac; 0.005 μM for G), a very good reproducibility (both: intra‐; inter‐electrodes reproducibility RSD % ranging from 0.3–0.5 for Ac; and 0.50–0.85 for G) and a very fast response time (6 s for Ac; 5 s in the case of G). In addition, high selectivity is obtained at FB‐SPEs, meaning that the FB‐SPEs electrochemical transducers are suitable to simultaneously quantify Ac and G in real samples, having several different (highly concentrated) interference.