Brain‐inspired electronics with multimodal signal processing have been investigated as the next‐generation semiconductor platforms owing to the limitations of von Neumann architecture, which limits data processing and energy consumption efficiencies. This study demonstrates the molecular reconfiguration of plasticity of artificial synaptic devices with tunable electric conductance based on molecular dynamics at the channel surfaces for realizing chemical multimodality. Carrier transport dynamics are adjusted using the density of trapped carriers for the molecular adsorption of HS in the MoSe2 channel, and the results are consistent with the molecular simulations. In molecular dynamics‐controlled devices, enhanced hysteresis enables the engineering of artificial neuroplasticity, mimicking the neurotransmitter release of biological synapses. Owing to the molecular reconfigurability of MoSe2 devices, the synaptic weights of excitatory and inhibitory synapse modes are significantly enhanced. Thus, this study can potentially contribute to the creation of the next generation of multimodal interfaces and artificial intelligence hardware realization. Molecular adsorption at the surface of channels induces the pulling or repelling of carriers transferred across the 2D semiconductor channel, which enables bioinspired synaptic behavior owing to the trapping or de‐trapping of carriers. Molecularly reconfigurable surface engineering in MoSe2 FETs is employed to mimic and enhance the essential features of biological synapses using van der Waals interactions upon molecular adsorption.