A method and an architecture for accessing hardware devices in a computer system and the chipset thereof are provided. A bi-directional two-wired serial interface, for instance, a system management bus (SMB), is configured to connect an I/O device, such as a local area network adapter, to a system controller such as a southbridge or a northbridge chipset. The I/O device which includes a SMB master controller serves as a SMB master device for generating a clock signal and transmitting a data signal defined by the SMB protocol to the system controller according to the clock signal. The system controller which includes a PCI master and a SMB slave controller serves as a SMB slave device for receiving commands and data bytes in the data signal from the SMB master device to drive the PCI master to access the register block of peripherals and system memory of the computer system.