Medeiros began his musical career at the age of 10 when he helped his father entertain guests on his tour bus on the island of Kauai. At the age of 17 in 1987, Medeiros won a local radio talent contest in Hawaii when he performed a cover version of Michael Masser's "Nothing's Gonna Change My Love for You" which was subsequently produced into an album by a small local independent label. A visiting radio executive from KZZP in Phoenix, Arizona heard the song and took the record back to Phoenix, where, through word of mouth, it became a national hit. A massive worldwide hit, it reached #12 on the Billboard Hot 100 and spent 4 weeks at number one on the UK singles chart in July 1988.

In 1988, he recorded the single "Un Roman d'amitié (Friend You Give Me a Reason)", a successful duet in France with Elsa Lunghini. He also achieved a 1990 United States #1 hit duet with Bobby Brown entitled "She Ain't Worth It". He had another hit duet with Ray Parker, Jr. titled "All I'm Missing Is You" which peaked at #32.

In 1992 Glenn Medeiros recorded a duet with Thomas Anders (of Modern Talking fame) titled "Standing Alone" and shot a video.

Today, Medeiros is the host and performs at the Hale Koa Hotel's luau in Waikiki, and is a school teacher. He has taught music at St. Joseph's School in Waipahu, and 5th grade at Island Pacific Academy in Kapolei. Nowadays he works at Maryknoll High School teaching the 9th grade World History.

Glenn attended Leeward Community College in Pearl City, Hawaii. Glenn married his wife Tammy Armstrong in 1996. They have 2 children together: Chord Kaleohone Medeiros (born February 3, 2000) and a daughter Lyric Leolani Medeiros (born May 1, 2001). Glenn now teaches 10th grade U.S. History at Maryknoll High School in Honolulu, Hawai'i.