Biggar and Matavesi both missed the trip to Ulster last weekend, but they are available to face the Gallagher Premiership champions in a massive festive fixture.
That means George Furbank shifts to full-back in place of Ahsee Tuala, who is among the replacements.
Juarno Augustus returns to the starting line-up at No.8, having been on the bench in Belfast.
Saints can call on an experienced bench at Twickenham, with the likes of Tom Wood, Paul Hill and Rory Hutchinson all among the replacements.
Tommy Freeman, Teimana Harrison, Alex Moon and Taqele Naiyaravoro remain unavailable for selection.
As for Harlequins, they make five changes to the team that beat Cardiff Blues last weekend.
England props Joe Marler and Will Collier, second row Matt Symons, fly-half Will Edwards and wing Louis Lynagh are restored to the starting line-up.
That means Quins are without star man Marcus Smith for the clash with Saints.
Harlequins: Green; Lynagh, Marchant, Esterhuizen, Murley; Edwards, Care; Marler, Walker, Collier; Symons, Lewies (c); Lawday, Kenningham, Dombrandt.
Replacements: Musk, Garcia Botta, Kerrod, Tizard, Lamb, Gjaltema, Northmore, Jones.
Saints: Furbank; Sleightholme, Proctor, Dingwall, Skosan; Biggar, Mitchell; Waller, Matavesi, Painter; Ribbans, Ratuniyarawa; Lawes, Ludlam (c), Augustus.
Replacements: Haywood, Auterac, Hill, Coles, Wood, James, Hutchinson, Tuala.