Little, 18, is a left-arm fast bowler who has played only four T20s so far - two of them T20Is - and was part of the Ireland team in the Under-19 World Cup in New Zealand in January this year. McBrine, 25, is an offspinning allrounder who has already played 30 ODIs and 19 T20Is, though his last T20I was in March 2017.
Ireland have played only one T20I against India, back in 2009 at Trent Bridge during the World T20 that year. India won that game by eight wickets with 4.3 overs to spare, thanks to Zaheer Khan's 4 for 19.
The Ireland selectors have left out Barry McCarthy and Craig Young from the squad that took part in the recently concluded tri-series in Deventer, where Ireland won one match, lost two and tied one game.
Before the series against India, Ireland will play a T20 against Sussex Sharks at the Arundel Castle Cricket Ground on June 24, which will also be Ed Joyce's testimonial match. Joyce announced his retirement after Ireland made their long-awaited Test debut.
Andrew White, the chairman of selectors, said the squad for the India matches had been chosen with a view to giving exposure to players for the future as well as being competitive, and the game against Sussex would help finalise Ireland's XI.
"The selectors have chosen what we believe to be a strong, in-form squad for this format of the game that balances experience with youth," White said. "Our deliberations were around finding a side that was competitive now, but with an eye on the future.
"Many in the squad will be either travelling to Sussex this weekend for the Ed Joyce Testimonial match on Sunday, or will be re-joining the senior squad from their English County sides. We had a good look at a number of players on the recent tri-series in the Netherlands and this weekend's match in Sussex will firm up the decisions made on the final playing eleven for the first fixture on Wednesday."
White identified building a good group of players for the World T20 qualifiers as one of the aims.
"We will continue our approach of providing opportunities for a wider pool of players to gain experience in T20 cricket on the international stage," he said. "With around 12 months to go to the World T20 Cup qualifiers, we are looking to build a competitive squad for that qualification stage and hopefully propel us into the main tournament in 2020."