Located on the Loddon Valley Highway, the town is 201 kilometres north west of the state capital, Melbourne and 51 kilometres north west of the regional centre, Bendigo.

Serpentine is in the Shire of Loddon local government area and, including the surrounding state suburb, had a population of 192 at the 2016 census.

[1] The town is named for Serpentine Creek, a tributary of the Loddon River.

Today, Serpentine is a producer of grain and cattle and a popular place for anglers.

The Burke and Wills expedition is alleged to have passed the townsite in 1860 while attempting to reach the Gulf of Carpentaria.