On Sunday, the 51-year-old actor arrived at the event in an all-black tailored ensemble comprising a blazer and flared trousers.
She accessorised the look with a belt tied around her waist and a pair of Dr Martens boots.
Applegate, who was diagnosed with multiple scleorisis (MS) in 2021, also brought a walking stick to the event and was accompanied by her daughter, Sadie Grace LeNoble.
The actress also flashed her nails to the camera, revealing that she had painted them a deep blue shade with the words “Jen” and “Judy” written on them in gold, in honour of her character, Jen, and that of her co-star’s, played by Linda Cardellini.
The appearance marked Applegate’s first award show since her MS diagnosis.
“So this Sunday will be the first awards show I have been to since 2019. And the first since MS,” she wrote on Twitter ahead of the event. “NERVOUS! But grateful to the @CriticsChoice for including me.”
The actor made her first public appearance since the diagnosis last year as she was honoured with a star on the Hollywood Walk of Fame.
Delivering a speech at the event in November, Applegate said: “I’ve had a really interesting life… this day means more to me than you could possibly imagine,” adding that she couldn’t “stand for long”.
She also paid tribute to her daughter. “I’m blessed every day that I get to wake up and take you to school. You are my everything… thank you for standing by me through all of this,” she said.
Roughly 130,000 people in the UK have MS, which is a lifelong neurological condition where the immune system attacks the nervous system, causing a wide range of symptoms.