D'Souza is deeply religious and says that, she regularly attends Sunday Mass at St. Anne's Parish (Bandra), and whenever the family is home, a part of their evening is reserved for saying the rosary together. In an interview with The Times of India, she comments, "I keep a Novena every Wednesday at St. Michael's Church in Mahim." In an interview with Daily News and Analysis, she said that "My communication with God is conversational, [...] I'm God's favourite child; I believe that God has always been kind to me." Tabloids repeatedly linked D'Souza romantically with Ritesh Deshmukh, ever since they starred together in their debut film Tujhe Meri Kasam in 2003. They were reportedly ready to get engaged, but Ritesh's father, the then-Maharashtra Chief Minister, Vilasrao Deshmukh did not agree. D'Souza later denied any rumors of a relationship with Deshmukh, and responds that she had just friendly relations with him. However, the couple eventually got married on 3 February 2012, according to Marathi marriage traditions in a Hindu wedding ceremony, they had a church wedding the next day. The couple's first child, a son named Riaan, was born on 25 November 2014. Their second son was born on 1 June 2016.