Her first acting role was on the television series Freaks and Geeks (1999–2000). Since then, she had series-regular roles in several television series including Related (2005–2006), Party Down (2009–2010; 2023), Das Boot (2018), Castle Rock (2019), Truth Be Told (2019), Fatal Attraction (2023), and Zero Day (2025).
Caplan's film breakthrough came with her role as Janis Ian in Mean Girls (2004). Her other film appearances include My Best Friend's Girl (2008) Cloverfield (2008), Hot Tub Time Machine, 127 Hours (both 2010), Save the Date, Bachelorette (both 2012), The Interview (2014), Now You See Me 2, Allied (both 2016), and Cobweb (2023).
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