Gyllenhaal and the film's director Edward Zwick said they had no idea the Oscar-nominated screen legend was battling chronic lymphocytic leukemia at the time. They learned of it after their work together.
"I think part of her sickness is what made her live her life ... and really cherish the moments she had and cherish the people she was with," said Gyllenhaal while promoting the film in New York on Sunday. "And she did when she was with us, cherish those moments, and they made us all love her."
Gyllenhaal filmed with Clayburgh in September of 2009. Clayburgh, 66, died Friday at her home in Lakeville, Conn., after a 21-year battle with the disease.
Gyllenhaal credits Clayburgh's iconic portrayal of a divorcee in 1978's "An Unmarried Woman" with helping his own mother through divorce.
"It helped her through that time in a way that no other movie or anybody else had," he said.
"She left an indelible impression on me," he said. "You don't really need much time to work or meet somebody and know that they're really alive ... and when I heard that (she was sick) I just thought, you know there's that moment when you go like 'oh, like maybe that might be why she was so extraordinary.' And it makes me want to encourage people to wake up and live it like Jill did."
Zwick said directing Clayburgh was "a real privilege."
"Her legacy is an extraordinary kind of acting which is of the highest level of authenticity but also of comedy. She managed to do both those things at once," he said.
"Love and Other Drugs," opening Nov. 24, also stars Anne Hathaway as Maggie, a free-spirited artist suffering from early onset Parkinson's disease.