Van Dyke took a more dramatic turn in the 1990s. He starred in the popular crime drama Diagnosis Murder alongside his real-life son, Barry Van Dyke. Debuting in 1993, the series featured Van Dyke as Dr. Mark Sloan, a medical professional who helped the police solve crimes. The series ended in 2001, but Van Dyke didn't stay away from the small screen for long. He played another amateur detective in a series of TV movies, beginning with 2006's Murder 101. That same year, the actor appeared in the Ben Stiller comedy Night at the Museum.
In November 1959, Van Dyke made his Broadway debut in The Girls Against the Boys. He then played the lead role of Albert Peterson in Bye Bye Birdie, which ran from April 14, 1960, to October 7, 1961. In a May 2011 interview with Rachael Ray, Van Dyke said that when he auditioned for a smaller part in the show he had no experience as a dancer, and that after he sang his audition song he did an impromptu soft-shoe out of sheer nervousness. Gower Champion, the show's director and choreographer, was watching, and promptly went up on stage to inform Van Dyke he had the lead. An astonished Van Dyke protested that he could not dance, to which Champion replied: "We'll teach you". That musical won four Tony awards including Van Dyke's Best Featured Actor Tony, in 1961. In 1980, Van Dyke appeared as the title role in the first Broadway revival of The Music Man.