The Frasier actress will play Allison, the wife of D.B. Russell, played by Ted Danson, says The Hollywood Reporter.
Allison Russell grew up in a rich Golden State family but later rebelled and married the criminalist D.B. Russell.
Gilpin will make her debut in the current 12th season's finale episode, and will return for several episodes the following season.
Jaclyn Smith will also return in the season finale as Hodges's (Wallace Langham) mother Olivia.
Peri Gilpin recently guested as a difficult patient in ABC's Grey's Anatomy alongside Nia Vardalos.
The season 12 finale of CSI will air on Wednesday, May 9 at 9pm on CBS.