Plymouth are the only team to have beaten the Royals this season but they fell behind after 20 minutes when Little chipped keeper Romain Larrieu.
Reading sealed victory 12 minutes after half-time when Leroy Lita provided a perfect ball for Doyle to tap in.
Plymouth's best chances fell to Nick Chadwick, who hit the bar as the hosts tried to recover.
Reading manager Steve Coppell on the quality and timing of Glenn Little's goal:
"It was a terrific individual goal amongst a scrappy first 45 minutes, the goal shone out like a beacon.
"It was a good piece of skill from Nick Chadwick to check back inside and Marcus Hahnemann, who's been critical here for us, made another key save.
"It could well be the game turned on that. If they had scored then it might have been a different fixture."
Plymouth: Larrieu, Barness, Doumbe, Ward, Aljofree, Buzsaky (Djordjic 45), Jarrett, Norris, Capaldi, Evans (Derbyshire 81), Chadwick.
Subs Not Used: Brevett, Lasley, McCormick.
Booked: Buzsaky, Aljofree.
Reading: Hahnemann, Murty, Sonko, Ingimarsson, Shorey, Little (Oster 82), Sidwell, Harper, Convey (Hunt 84), Doyle (Cox 90), Lita.
Subs Not Used: Stack, Makin.
Booked: Sidwell, Doyle.
Goals: Little 20, Doyle 57.
Ref: K Wright (Cambridgeshire).