A multi-channel transient voltage suppression device includes a semiconductor substrate, a semiconductor layer, at least two bidirectional transient voltage suppression structures, and at least one isolation trench. The semiconductor substrate, having a first conductivity type, is coupled to a grounding terminal. The semiconductor layer, having a second conductivity type opposite to the first conductivity type, is formed on the semiconductor substrate. The bidirectional transient voltage suppression structures are formed in the semiconductor layer. Each bidirectional transient voltage suppression structure is coupled to an input/output (I/O) pin and the grounding terminal. The isolation trench is formed in the semiconductor substrate and the semiconductor layer and formed between the bidirectional transient voltage suppression structures. The isolation trench has a height larger than the height of the semiconductor layer and surrounds the bidirectional transient voltage suppression structures.