Guadalupe Creek or Guadalupe Valley Creek is a short eastward-flowing stream whose watershed originates just east of the highest peak of San Bruno Mountain in San Mateo County, California, United States.

The confluence of Devil's Arroyo and Wax Myrtle Ravine is at the head of the Guadalupe Valley at elevation 200 feet, where the Guadalupe Creek mainstem flows eastward largely confined to underground pipes and ditches, emerging to daylight just east of Bayshore Boulevard.

This lagoon is a remnant of San Francisco Bay, formed by the construction of the U. S. Highway 101 causeway, and became diminished when its north and central portions (which are now crossed by Visitacion Creek) were filled with garbage and landfill.

It drains the area bounded by Bayview Hill (by Candlestick Park), McLaren Ridge and San Bruno Mountain.

San Bruno Mountain hosts several endangered species and the Guadalupe Valley provides habitat for the Mission blue (Aricia icarioides missionensis), elfin (Callophrys mossii bayensis) and callippe silverspot (Speyeria callippe callippe) butterflies, as well as the San Francisco garter snake (Thamnophis sirtalis tetrataenia).