Coolio's longtime manager Jarez Posey said the rapper died on Wednesday at a friend's house in Los Angeles.
He had excused himself to use the bathroom but when he didn't return, the friend went to check on him and found him unresponsive and laying on the floor.
Paramedics were called but were unable to revive the star, with cardiac arrest the suspected cause of death.
Gangsta's Paradise hit the number one spot in countries worldwide and became the top-selling single of 1995 in the US, shifting more than five million copies.
Coolio would go on to win a Grammy and two MTV Video Music Awards for the hit which samples Stevie Wonder's 1976 song Pastime Paradise.