Reina looks set to reunite with former Liverpool manager Rafael Benitez on a season-long loan deal while Real Madrid striker Higuain, 25, is set to move to the Stadio San Paolo for a reported 40million euro (£34.5million) fee on permanent deal.
Both players will be presented as Napoli players on Monday, Higuain despite reports earlier this summer linking him with Arsenal.
Reina's agent Manuel Garcia Quilon said: "He's happy to reunite with Benitez because he's known him for over five years from their time in Spain and England, and they worked very well together."
The Spain international's chances of first-team football at Anfield appeared increasingly limited following the arrival of £9m Simon Mignolet from Sunderland.
Benitez has already signed winger Dries Mertens from PSV Eindhoven and both forward Jose Callejon and defender Raul Albiol from Real as the Serie A runners-up rebuild for a title challenge by reinvesting the reported 64m euros (£55m) earned from striker Edinson Cavani's transfer to Paris St Germain.