Here, 2D Siloxene nanosheets are newly applied to functionalize porous laser-induced graphene (LIG) on polydimethylsiloxane, modify the surface chemical properties of LIG, and improve the heterogeneous electron transfer rate. Meanwhile, the newly generated COSi crosslink boosts the binding of LIG and Siloxene. Thus, the Siloxene/LIG composite is used as the basic electrode material for the multifunctional detection of copper (Cu) ions, pH, and temperature in human perspiration. Moreover, to enhance the sensing performance of Cu ions, Siloxene/LIG is further modified by carbon nanotubes (CNTs). The fabricated Siloxene-CNT/LIG-based Cu-ion sensor shows linear response within a wide range of 10–500 ppb and a low detection limit of 1.55 ppb. In addition, a pH sensor is integrated to calibrate for determining the accurate concentration of Cu ions due to pH dependency of the Cu-ion sensor. The polyaniline-deposited pH sensor demonstrates a good sensitivity of −64.81 mV pH−1 over the pH range of 3–10. Furthermore, a temperature sensor for accurate skin temperature monitoring is also integrated and exhibits a stable linear resistance response with an excellent sensitivity of 9.147 Ω °C−1 (correlation coefficient of 0.139% °C−1). The flexible hybrid sensor is promising in applications of noninvasive heavy-metal ion detection and prediction of related diseases.