A three-member bench of the Supreme Court led by Chief Justice Dipak Misra dismissed a petition filed by the men to review a 2017 order by the top court, which had confirmed the death penalty given to them by the Delhi High Court.
Holding that the crime committed on a moving bus was in the "rarest of rare category", the court noted that the girl and her male friend were brutally assaulted, her abdomen ripped apart with an iron rod and internal organs pulled out.
They were thrown out of the bus moving at a high speed and the accused tried to run the vehicle over them. She was left on the road half-naked, seriously injured, severely bleeding and shivering in the winter chill.
The judge had convicted Mukesh Singh, 26, Vinay Sharma, 20, Pawan Gupta, 19, and Akshay Thakur, 28, on September 10, holding that there was strong evidence they had committed the brutal gang-rape and a "cold-blooded murder".
Their underage accomplice, who had turned 18, was sent to a reform home for three years after a juvenile board handed down a guilty verdict on August 31.
The main accused in the case Ram Singh was found hanging in his Tihar jail cell on March 11, 2013.
The brutal gang-rape on the night of December 16, 2012 had sparked spontaneous public outrage across India, bringing thousands of people onto streets in protest against authorities' failure to ensure women's safety.
It also triggered uproar in Parliament and prompted the government to enact a tough law to deal with crimes against women, increased policing and fast-tracking of rape cases across the country.
After the savage attack, the young woman, a paramedical student, fought bravely for life and was airlifted to Singapore for treatment. But her injuries left her with no real chance and she died on December 29, 2012.
The court mainly relied on the three dying declarations of the victim, the statement of her male friend, DNA analysis, forensic and electronic evidence to hold them guilty.